| 1. |
- Wiszmeg, Andréa, et al.
(författare)
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Transforming trash to treasure Cultural ambiguity in foetal cell research
- 2021
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Ingår i: Philosophy Ethics and Humanities in Medicine. - : Springer Science and Business Media LLC. - 1747-5341. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Rich in different kind of potent cells, embryos are used in modern regenerative medicine and research. Neurobiologists today are pushing the boundaries for what can be done with embryos existing in the transitory margins of medicine. Therefore, there is a growing need to develop conceptual frameworks for interpreting the transformative cultural, biological and technical processes involving these aborted, donated and marginal embryos. This article is a contribution to this development of frameworks. Methods This article examines different emotional, cognitive and discursive strategies used by neurobiologists in a foetal cell transplantation trial in Parkinson's disease research, using cells harvested from aborted embryos. Two interviews were analysed in the light of former observations in the processing laboratories, using the anthropologist Mary Douglas's concept of pollution behaviour and the linguist, philosopher, psychoanalyst and feminist Julia Kristeva's concept of the abjective to explain and make sense of the findings. Results The findings indicate that the labour performed by the researchers in the trial work involves transforming the foetal material practically, as well as culturally, from trash to treasure. The transformation process contains different phases, and in the interview material we observed that the foetal material or cells were considered objects, subjects or rejected as abject by the researchers handling them, depending on what phase of process or practice they referred to or had experience of. As demonstrated in the analysis, it is the human origin of the cell that makes it abjective and activates pollution discourse, when the researchers talk of their practice. Conclusions The marginal and ambiguous status of the embryo that emerges in the accounts turns the scientists handling foetal cells into liminal characters in modern medicine. Focusing on how practical as well as emotional and cultural strategies and rationalizations of the researchers emerge in interview accounts, this study adds insights on the rationale of practically procuring, transforming and utilizing the foetal material to the already existing studies focused on the donations. We also discuss why the use and refinement of a tissue, around which there is practical consensus but cultural ambiguity, deserves further investigation.
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| 2. |
- Isaksson, Simon, 1988, et al.
(författare)
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Protein-Containing Lipid Bilayers Intercalated with Size-Matched Mesoporous Silica Thin Films
- 2017
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 17:1, s. 476-485
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Tidskriftsartikel (refereegranskat)abstract
- Proteins are key components in a multitude of biological processes, of which the functions carried out by transmembrane (membrane-spanning) proteins are especially demanding for investigations. This is because this class of protein needs to be incorporated into a lipid bilayer representing its native environment, and in addition, many experimental conditions also require a solid support for stabilization and analytical purposes. The solid support substrate may, however, limit the protein functionality due to protein material interactions and a lack of physical space. We have in this work tailored the pore size and pore ordering of a mesoporous silica thin film to match the native cell-membrane arrangement of the transmembrane protein human aquaporin 4 (hAQP4). Using neutron reflectivity (NR), we provide evidence of how substrate pores host the bulky water-soluble domain of hAQP4, which is shown to extend 7.2 nm into the pores of the substrate. Complementary surface analytical tools, including quartz crystal microbalance with dissipation monitoring (QCM-D) and fluorescence microscopy, revealed successful protein-containing supported lipid bilayer (pSLB) formation on mesoporous silica substrates, whereas pSLB formation was hampered on nonporous silica. Additionally, electron microscopy (TEM and SEM), light scattering (DLS and stopped-flow), and small-angle X-ray scattering (SAXS) were employed to provide a comprehensive characterization of this novel hybrid organic-inorganic interface, the tailoring of which is likely to be generally applicable to improve the function and stability of a broad range of membrane proteins containing water-soluble domains.
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| 3. |
- Peruzzi, Niccolò, et al.
(författare)
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Multimodal ex vivo methods reveal that Gd-rich corrosion byproducts remain at the implant site of biodegradable Mg-Gd screws
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 136, s. 582-591
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Tidskriftsartikel (refereegranskat)abstract
- Extensive research is being conducted on magnesium (Mg) alloys for bone implant manufacturing, due to their biocompatibility, biodegradability and mechanical properties. Gadolinium (Gd) is among the most promising alloying elements for property control in Mg alloy implants; however, its toxicity is controversial. Investigating Gd behavior during implant corrosion is thus of utmost importance. In this study, we analyzed the degradation byproducts at the implant site of biodegradable Mg-5Gd and Mg-10Gd implants after 12 weeks healing time, using a combination of different imaging techniques: histology, energy-dispersive x-ray spectroscopy (EDX), x-ray microcomputed tomography (µCT) and neutron µCT. The main finding has been that, at the healing time in exam, the corrosion appears to have involved only the Mg component, which has been substituted by calcium and phosphorus, while the Gd remains localized at the implant site. This was observed in 2D by means of EDX maps and extended to 3D with a novel application of neutron tomography. X-ray fluorescence analysis of the main excretory organs also did not reveal any measurable accumulation of Gd, further reinforcing the conclusion that very limited or no removal at all of Gd-alloy happened during degradation.
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| 4. |
- Cabaleiro-Lago, Celia, et al.
(författare)
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Recent Advances in Molecularly Imprinted Polymers and Their Disease-Related Applications
- 2023
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Ingår i: Polymers. - : MDPI. - 2073-4360. ; 15:21, s. 4199-4199
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Forskningsöversikt (refereegranskat)abstract
- Molecularly imprinted polymers (MIPs) and the imprinting technique provide polymeric material with recognition elements similar to natural antibodies. The template of choice (i.e., the antigen) can be almost any type of smaller or larger molecule, protein, or even tissue. There are various formats of MIPs developed for different medical purposes, such as targeting, imaging, assay diagnostics, and biomarker detection. Biologically applied MIPs are widely used and currently developed for medical applications, and targeting the antigen with MIPs can also help in personalized medicine. The synthetic recognition sites of the MIPs can be tailor-made to function as analytics, diagnostics, and drug delivery systems. This review will cover the promising clinical applications of different MIP systems recently developed for disease diagnosis and treatment.
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| 5. |
- Alenezi, Ali, et al.
(författare)
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Osseointegration effects of local release of strontium ranelate from implant surfaces in rats
- 2019
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Ingår i: Journal of Materials Science: Materials in Medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 30:10, s. 116-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : Numerous studies have reported the beneficial effects of strontium on bone growth, particularly by stimulating osteoblast proliferation and differentiation. Thus, strontium release around implants has been suggested as one possible strategy to enhance implant osseointegration. AIM : This study aimed to evaluate whether the local release of strontium ranelate (Sr-ranelate) from implants coated with mesoporous titania could improve bone formation around implants in an animal model. MATERIALS AND METHODS : Mesoporous titania (MT) thin coatings were formed utilizing the evaporation induced self-assembly (EISA) method using Pluronic (P123) with or without the addition of poly propylene glycol (PPG) to create materials with two different pore sizes. The MT was deposited on disks and mini-screws, both made of cp Ti grade IV. Scanning electron microscopy (SEM) was performed to characterize the MT using a Leo Ultra55 FEG instrument (Zeiss, Oberkochen, Germany). The MT was loaded with Sr-ranelate using soaking and the drug uptake and release kinetics to and from the surfaces were evaluated using quartz crystal microbalance with dissipation monitoring (QCM-D) utilizing a Q-sense E4 instrument. For the in vivo experiment, 24 adult rats were analyzed at two time points of implant healing (2 and 6 weeks). Titanium implants shaped as mini screws were coated with MT films and divided into two groups; supplied with Sr-ranelate (test group) and without Sr-ranelate (control group). Four implants (both test and control) were inserted in the tibia of each rat. The in vivo study was evaluated using histomorphometric analyses of the implant/bone interphase using optical microscopy. RESULTS : SEM images showed the successful formation of evenly distributed MT films covering the entire surface with pore sizes of 6 and 7.2 nm, respectively. The QCM-D analysis revealed an absorption of 3300 ng/cm2 of Sr-ranelate on the 7.2 nm MT, which was about 3 times more than the observed amount on the 6 nm MT (1200 ng/cm2). Both groups showed sustained release of Sr-ranelate from MT coated disks. The histomorphometric analysis revealed no significant differences in bone implant contact (BIC) and bone area (BA) between the implants with Sr-ranelate and implants in the control groups after 2 and 6 weeks of healing (BIC with a p-value of 0.43 after 2 weeks and 0.172 after 6 weeks; BA with a p-value of 0.503 after 2 weeks, and 0.088 after 6 weeks). The mean BIC and BA values within the same group showed significant increase among all groups between 2 and 6 weeks. CONCLUSION : This study could not confirm any positive effects of Sr-ranelate on implant osseointegration.
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| 6. |
- Olsson, Pär A T, 1981-, et al.
(författare)
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Ab initio investigation of monoclinic phase stability and martensitic transformation in crystalline polyethylene
- 2018
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Ingår i: Physical Review Materials. - : American Physical Society. - 2475-9953. ; 2:7, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- We study the phase stability and martensitic transformation of orthorhombic and monoclimic polyethylene by means of density functional theory using the nonempirical consistent-exchange vdW-DF-cx functional [Phys. Rev. B 89, 035412 (2014)]. The results show that the orthorhombic phase is the most stable of the two. Owing to the occurrence of soft librational phonon modes, the monoclimic phase is predicted not to be stable at zero pressure and temperature, but becomes stable when subjected to compressive transverse deformations that pin the chains and prevent them from wiggling freely. This theoretical characterization, or prediction, is consistent with the fact that the monoclimic phase is only observed experimentally when the material is subjected to mechanical loading. Also, the estimated threshold energy for the combination of lattice deformation associated with the T1 and T2 transformation paths (between the orthorhombic and monoclimic phases) and chain shuffling is found to be sufficiently low for thermally activated back transformations to occur. Thus, our prediction is that the crystalline part can transform back from the monoclimc to the orthorhombic phase upon unloading and/or annealing, which is consistent with experimental observations. Finally, we observe how a combination of such phase transformations can lead to a fold-plane reorientation from {110} to {100} type in a single orthorhombic crystal.
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| 7. |
- Albèr, Cathrine, et al.
(författare)
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Effects of water gradients and use of urea on skin ultrastructure evaluated by confocal Raman microspectroscopy
- 2013
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier. - 0005-2736 .- 1879-2642 .- 0006-3002. ; 1828:11, s. 2470-2478
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Tidskriftsartikel (refereegranskat)abstract
- The rather thin outermost layer of the mammalian skin, stratum corneum (SC), is a complex biomembrane which separates the water rich inside of the body from the dry outside. The skin surface can be exposed to rather extreme variations in ambient conditions (e.g. water activity, temperature and pH), with potential effects on the barrier function. Increased understanding of how the barrier is affected by such changes is highly relevant for regulation of transdermal uptake of exogenous chemicals. In the present study we investigate the effect of hydration and the use of a well-known humectant, urea, on skin barrier ultrastructure by means of confocal Raman microspectroscopy. We also perform dynamic vapor sorption (DVS) microbalance measurements to examine the water uptake capacity of SC pretreated with urea. Based on novel Raman images, constructed from 2D spectral maps, we can distinguish large water inclusions within the skin membrane exceeding the size of fully hydrated corneocytes. We show that these inclusions contain water with spectral properties similar to that of bulk water. The results furthermore show that the ambient water activity has an important impact on the formation of these water inclusions as well as on the hydration profile across the membrane. Urea significantly increases the water uptake when present in skin, as compared to skin without urea, and it promotes formation of larger water inclusions in the tissue. The results confirm that urea can be used as a humectant to increase skin hydration.
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| 8. |
- Sun, Lingbo, et al.
(författare)
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Installation of O-glycan sulfation capacities in human HEK293 cells for display of sulfated mucins
- 2021
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Ingår i: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 298:2
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Tidskriftsartikel (refereegranskat)abstract
- The human genome contains at least 35 genes that encode Golgi sulfotransferases that function in the secretory pathway, where they are involved in decorating glycosaminoglycans, glycolipids, and glycoproteins with sulfate groups. Although a number of important interactions by proteins such as Selectins, Galectins, and Siglecs are thought to mainly rely on sulfated O-glycans, our insight into the sulfotransferases that modify these glycoproteins, and in particular GalNAc-type O-glycoproteins, is limited. Moreover, sulfated mucins appear to accumulate in respiratory diseases, arthritis, and cancer. To explore further the genetic and biosynthetic regulation of sulfated O-glycans, here we expanded a cell-based glycan array in the human HEK293 cell line with sulfation capacities. We stably engineered O-glycan sulfation capacities in HEK293 cells by site-directed knock-in of sulfotransferase genes in combination with knockout of genes to eliminate endogenous O-glycan branching (core2 synthase gene GCNT1) and/or sialylation capacities in order to provide simplified substrates (core1 Galβ1-3GalNAcα1-O-Ser/Thr) for the introduced sulfotransferases. Expression of the galactose 3O-sulfotransferase 2 (GAL3ST2) in HEK293 cells resulted in sulfation of core1 and core2 O-glycans, whereas expression of galactose 3O-sulfotransferase 4 (GAL3ST4) resulted in sulfation of core1 only. We used the engineered cell library to dissect the binding specificity of galectin-4 and confirmed binding to the 3-O-sulfo-core1 O-glycan. This is a first step towards expanding the emerging cell-based glycan arrays with the important sulfation modification for display and production of glycoconjugates with sulfated O-glycans.
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| 9. |
- De Silva, Kushan, et al.
(författare)
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Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans : a bioinformatics analytic workflow
- 2022
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Ingår i: Functional & Integrative Genomics. - : Springer Science and Business Media LLC. - 1438-793X .- 1438-7948. ; 22:5, s. 1003-1029
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) has a complex etiology which is not yet fully elucidated. The identification of gene perturbations and hub genes of T2D may deepen our understanding of its genetic basis. We aimed to identify highly perturbed genes and hub genes associated with T2D via an extensive bioinformatics analytic workflow consisting of five steps: systematic review of Gene Expression Omnibus and associated literature; identification and classification of differentially expressed genes (DEGs); identification of highly perturbed genes via meta-analysis; identification of hub genes via network analysis; and downstream analysis of highly perturbed genes and hub genes. Three meta-analytic strategies, random effects model, vote-counting approach, and p value combining approach, were applied. Hub genes were defined as those nodes having above-average betweenness, closeness, and degree in the network. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19-related gene sets, and Genotype-Tissue Expression profiles. Analysis of 27 eligible microarrays identified 6284 DEGs (4592 downregulated and 1692 upregulated) in four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Analyses revealed 79 highly perturbed genes and 28 hub genes. Downstream analyses identified enrichments of shared genes with certain other diabetes phenotypes; insulin synthesis and action-related pathways and metabolomics; mechanistic associations with apoptosis and immunity-related pathways; COVID-19-related gene sets; and cell types demonstrating over- and under-expression of marker genes of T2D. Our approach provided valuable insights on T2D pathogenesis and pathophysiological manifestations. Broader utility of this pipeline beyond T2D is envisaged.
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| 10. |
- Zhang, Yuecheng
(författare)
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Glycosylation in cancer and infection : the role of sialic acid
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sialic acids (SA), a group of nine-carbon backbone monosaccharides are abundantly expressed in vertebrates. They are usually linked to the terminal of glycan chains and play crucial roles in many biological processes, including cell adhesion, cell-cell interactions, immune modulation, cancer cell migration and invasion, as well as viral infections. To analyze and monitor SA expression, antibodies and glycan-binding lectins are typically used. However, high costs and poor stability limit the application in SA analysis. To overcome these drawbacks, an imprinting technique was used to synthesize an alternative SA receptor – SA molecularly imprinted polymers (SA-MIPs). Fluorescent molecules are embedded into the MIPs, facilitating the detection of MIPs binding to cells by flow cytometry and fluorescence microscopy. Firstly, core-shell SA imprinted MIPs were used to analyze SA expression in a panel of breast cancer cell lines. The SA expression of these cell lines was also tested by using the two glycan-binding lectins, MAL andSNA, which recognize α2,3 and α2,6 SA, respectively. Our results show that breast cancer cell lines express α2,3 and α2,6 SA dissimilarly, and hence present different SA-MIP binding patterns. The specificity of SA-MIPs was further verified by an inhibition assay using two pentavalent SA conjugates that interfere with the SAMIPs.Furthermore, the SA-MIP synthesis protocol has been improved by using silica-coated polystyrene particles. The polystyrene core particles are lighter and smaller, increasing MIP suspensibility and augmenting MIP-cancer cell interactions. The cancer cell binding properties and the specificity have been verified by using thirteen different cancer cell lines, showing that the SA-MIPs can be used as effective tools for SA expression analysis. The SA-MIPs were used to analyze the SA expression of in vitro cultured cells treated with soluble cytokines to mimic the tumor microenvironment. The SA expression of two cancer cell lines stimulated with soluble cytokines was analyzed by using lectins and SA-MIPs. The MIPbinding data correlated well with lectin staining results, demonstrating the potential of SA-MIPs to be used in the analysis of overexpressed SA in the tumor microenvironment. Furthermore, the involvement of SA in the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed. The viral surface receptor-binding domain (RBD) recognizes and conjugates with receptors on host cells, triggering the infection. Although the interaction between the RBD and host cells has been extensively studied, the mechanism behind this reaction is not fully determined. In this study, the interaction between the viral RBD and a panel of human cell lines from tissues susceptible to viral infection was tested. Moreover, the role of SA in this interaction has also been tested and evaluated.
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