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- Classen, Jean-Francois, et al.
(författare)
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Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1137-1144
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Systemic sclerosis (SSc) is a severe connective tissue disease of unknown etiology, characterized by fibrosis of the skin and multiple internal organs. Recent findings suggested that the disease is driven by stimulatory autoantibodies to platelet-derived growth factor receptor (PDGFR), which stimulate the production of reactive oxygen species (ROS) and collagen by fibroblasts. These results opened novel avenues of research into the diagnosis and treatment of SSc. The present study was undertaken to confirm the presence of anti-PDGFR antibodies in patients with SSc. METHODS: Immunoglobulins from 37 patients with SSc were purified by protein A/G chromatography. PDGFR activation was tested using 4 different sensitive bioassays, i.e., cell proliferation, ROS production, signal transduction, and receptor phosphorylation; the latter was also tested in a separate population of 7 patients with SSc from a different research center. RESULTS: Purified IgG samples from patients with SSc were positive when tested for antinuclear autoantibodies, but did not specifically activate PDGFRalpha or PDGFRbeta in any of the tests. Cell stimulation with PDGF itself consistently produced a strong signal. CONCLUSION: The present results raise questions regarding the existence of agonistic autoantibodies to PDGFR in SSc.
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- Fischer, Gerhard, 1978, et al.
(författare)
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Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism.
- 2009
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Aquaporins are transmembrane proteins that facilitate the flow of water through cellular membranes. An unusual characteristic of yeast aquaporins is that they frequently contain an extended N terminus of unknown function. Here we present the X-ray structure of the yeast aquaporin Aqy1 from Pichia pastoris at 1.15 A resolution. Our crystal structure reveals that the water channel is closed by the N terminus, which arranges as a tightly wound helical bundle, with Tyr31 forming H-bond interactions to a water molecule within the pore and thereby occluding the channel entrance. Nevertheless, functional assays show that Aqy1 has appreciable water transport activity that aids survival during rapid freezing of P. pastoris. These findings establish that Aqy1 is a gated water channel. Mutational studies in combination with molecular dynamics simulations imply that gating may be regulated by a combination of phosphorylation and mechanosensitivity.
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- Kloss, Frank, et al.
(författare)
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The role of oxygen termination of nanocrystalline diamond on immobilisation of BMP-2 and subsequent bone formation
- 2008
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 29:16, s. 2433-2442
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Tidskriftsartikel (refereegranskat)abstract
- Medical implants are increasingly often inserted into bone of frail patients, who are advanced in years. Due to age, severe trauma or pathology-related bone changes, osseous healing at the implant site is frequently limited. We were able to demonstrate that coating of endosseous implants with nanocrystalline diamond (NCD) allows stable functionalization by means of physisorption with BMP-2. Strong physisorption was shown to be directly related to the unique properties of NCD, and BMP-2 in its active form interacted strongly when NCD was oxygen-terminated. The binding of the protein was monitored under physiological conditions by single molecule force spectroscopy, and the respective adsorption energies were further substantiated by force-field-calculations. Implant surfaces refined in such a manner yielded enhanced osseointegration in vivo, when inserted into sheep calvaria. Our results further suggest that this technical advancement can be readily applied in clinical therapies with regard to bone healing, since primary human mesenchymal stromal cells strongly activated the expression of osteogenic markers when being cultivated on NCD physisorbed with physiological amounts of BMP-2.
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- Löf, David, et al.
(författare)
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Structural Characterization of Nonionic Mixed Micelles Formed by C(12)EO(6) Surfactant and P123 Triblock Copolymer.
- 2009
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 113:16, s. 5478-5486
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Tidskriftsartikel (refereegranskat)abstract
- A structural characterization of mixed micelles formed in aqueous solution by the PEO-PPO-PEO triblock copolymer P123 and the nonionic surfactant C(12)EO(6) was carried out using various techniques, including ultralow shear viscosimetry, depolarized dynamic light scattering (VH-DLS), depolarized static light scattering (VH-SLS), and small-angle X-ray scattering (SAXS). The sphere-to-rod transition of the mixed micelles was studied in a diluted regime (P123 concentrations ranging from 0.5 to 10 wt %) at C(12)EO(6)/P123 molar ratios of 2.2, 3.2, 6.0, and 11 as well as for the pure C(12)EO(6). The data from VH-SLS and viscosimetry displayed a sharp increase in the intensity and viscosity, respectively, at the sphere-to-rod transition, and the results from the two methods were in accordance. In both techniques, an increased transition temperature with increasing content of C(12)EO(6) (in the molar ratio regime from 2.2 to 11) was observed. SAXS was used as the main technique, and a thorough structural characterization was performed, where indirect Fourier transformation (IFT) and generalized indirect Fourier transformation (GIFT) were employed in the analysis procedure of the SAXS data. The p(r) functions obtained from the IFT (employed at low P123 concentrations, i.e., 1.0 and 2.0 wt %) and GIFT (employed above 2.0 wt %) analyses revealed increased inhomogeneities in the mixed micelles when the molar ratio was increased. This suggested that the C(12)EO(6) organized themselves at the interface between the PPO core and the PEO corona of the P123 micelles, with the C(12) alkyl chain stretching into the hydrophobic core and the EO(6) part residing in the hydrophilic corona. The structure factor parameters obtained with GIFT for a molar ratio of 2.2 at a P123 concentration of 5.0 wt % showed radius values smaller than what was estimated from the p(r) functions. This was explained by an interpenetration of the PEO chains from one mixed micelle into a neighboring one. VH-DLS was performed on the mixed micelles at a temperature 3 degrees C above the transition temperature and at a molar ratio of 2.2. From the analyzed data, the average length L of the rods was estimated to be 102 nm.
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- Naghsh, Amir, et al.
(författare)
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Distributed-PD: Challenges and Opportunities
- 2008
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Ingår i: Proceedings of the Participatory Design Conference. - Bloomington : The Trustees of Indiana University. - 9780981856100 ; , s. 290-291
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Konferensbidrag (populärvet., debatt m.m.)abstract
- A limitation of Participatory Design (PD) is that it has primarily been focused on project stakeholders being co-located, whereas in recent years we are starting to see software development projects involve more distributed collaborations. This panel grows out of the issues raised from a series of workshops on Distributed Participatory Design (http://www.distributedpd.com) and discusses the experiences and challenges of performing PD in distributed design teams.
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- Olsson, Erik, et al.
(författare)
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Everyday memory self-assessed by adult patients with acquired brain damage and their significant others.
- 2006
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Ingår i: Neuropsychol Rehabil. - 0960-2011 .- 1464-0694. ; 16:3, s. 257-71
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Tidskriftsartikel (refereegranskat)abstract
- Self-assessment of everyday memory dysfunction was examined in a sample of 48 patients with acquired brain injury. A modified version of the Everyday Memory Questionnaire (EMQ20) was used as an interview. Patients were compared to 30 persons without brain injury. EMQ20 was completed by significant others (SOs) to both patients and controls. Patients reported a higher frequency of memory problems (days per week) and more distress due to memory deficits compared to controls. A high degree of consistency was found between patient and SO ratings on these measures. No difference was found on the total usage of memory aids, but patients asked other people more for a reminder and used loose notes less than controls. Implications for rehabilitation and future research are discussed.
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- Tikkanen, Karin, 1979-
(författare)
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A Comparative Grammar of Latin and the Sabellian Languages : The System of Case Syntax
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation is a comparative grammar of the case syntax of Latin and the Sabellian languages. The Sabellian languages were a group of Indo-European languages on the Italian peninsula, attested in inscriptions approx. 650 – 50 BCE. The main question of the study concerns the ultimate relationship between Latin and the Sabellian languages, considering the large number of similarities found within these linguistic systems, in all areas of language. According to some scholars these similarities should be ascribed to the fact that the languages in question were spoken in the same area, the geographically limited region of the Italian peninsula, for a long time. According to others, the similarities are such that we have to assume a common Proto-Italic language stage after the split from Western Proto-Indo-European. Earlier research into this problem has traditionally focused on the more common areas within comparative and historical linguistics, that is the vocabulary, the phonology and the morphology. This thesis considers the structures of syntax, with a focus on case. The last attempts to describe the Sabellian case syntax are now over a century old and much new material has since then appeared. The system met with in the Sabellian material is compared to the data met with in other early Indo-European languages and especially to the Latin data. The extent to which the structures found in Latin and Sabellian are specific to these two languages and to what extent they represent their common Proto-Indo-European heritage is discussed. The evidence drawn from the syntactic comparison made in this work contributes towards establishing a hypothetical common Proto-Italic language stage.
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