| 1. |
- Cutas, Daniela, 1978, et al.
(författare)
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Legal imperialism in the regulation of stem cell research and therapy: the problem of extraterritorial jurisdiction
- 2010
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Ingår i: Capps BJ & Campbell AV (eds.). CONTESTED CELLS: Global Perspectives on the Stem Cell Debate. - London : Imperial College Press. - 9781848164376 ; , s. 95-119
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Countries worldwide have very different national regulations on human embryonic stem (ES) cell research, informed by a range of ethical values. Some countries find reason to extend the applicability of their regulations on such research to its citizens when they visit other countries. Extraterritorial jurisdiction has recently been identified as a potential challenge towards global regulation of ES cell research. This chapter explores the implications and impact of extraterritorial jurisdiction and global regulation of ES cell research on researchers, clinicians and national health systems, and how this may affect patients. The authors argue that it would make ethical sense for ES cell restrictive countries to extend its regulations on ES cell research beyond its borders, because, if these countries really consider embryo destruction to be objectionable on the basis on the status of the embryo, then they ought to count it morally on par with murder (and thus have a moral imperative to protect embryos from the actions of its own citizens). However, doing so could lead to a legal situation that would result in substantial harm to central values in areas besides research, such as health care, the job market, basic freedom of movement, and strategic international finance and politics. Thus, it seems that restrictive extraterritorial jurisdiction in respect to ES cell research would be deeply problematic, given that the ethical permissibility of ES cell research is characterised by deep and wide disagreement.
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| 2. |
- Johansson, Martin L, et al.
(författare)
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Non-invasive sampling procedure revealing the molecular events at different abutments of bone-anchored hearing systems–A prospective clinical pilot study
- 2022
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the molecular activities in different compartments around the bone-anchored hearing system (BAHS) with either electropolished or machined abutments and to correlate these activities with clinical and microbiological findings. Materials and methods: Twelve patients received machined or electropolished abutments after implant installation of BAHS. Peri-abutment fluid and tissue were collected from baseline to 12 months. Gene expression of cytokines and factors related to tissue healing and inflammation, regeneration and remodelling, as well as bacterial recognition were determined using quantitative-polymerase chain reaction (qPCR). The clinical status was evaluated using the Holgers scoring system, and bacterial colonisation was investigated by culturing. Results: The gene expression of inflammatory cytokines (IL-8, IL-1β, and IL-10) and bacteria-related Toll-like receptors (2 and 4) was higher in the peri-abutment fluid than at baseline and in the peri-abutment tissue at 3 and 12 months. Conversely, the expression of genes related to tissue regeneration (Coll1a1 and FOXO1) was higher in the tissue samples than in the peri-abutment fluid at 3 and 12 months. Electropolished abutments triggered higher expression of inflammatory cytokines (IL-8 and IL-1β) (in peri-abutment fluid) and regeneration factor FOXO1 (in peri-abutment tissue) than machined abutments. Several cytokine genes in the peri-abutment fluid correlated positively with the detection of aerobes, anaerobes and Staphylococcus species, as well as with high Holger scores. Conclusion: This study provides unprecedented molecular information on the biological processes of BAHS. Despite being apparently healed, the peri-abutment fluid harbours prolonged inflammatory activity in conjunction with the presence of different bacterial species. An electropolished abutment surface appears to be associated with stronger proinflammatory activity than that with a machined surface. The analysis of the peri-abutment fluid deserves further verification as a non-invasive sampling and diagnostic procedure of BAHS.
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| 3. |
- Carlberg, Björn, 1983
(författare)
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Integration of Electrospun Materials in Microelectronic and Biomedical Applications
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis demonstrates the use of electrospinning and the novel properties of electrospunmaterials in two fields.The microelectronics industry has identified thermal interface materials as one of themajor bottlenecks hindering further integration at packaging level. New concepts basedon metal-polymer composite architectures are needed to fulfill current and future thermaland thermomechanical requirements on thermal interface materials at maintained costefficiency. In this thesis, an interpenetrating phase polymer-metal composite for thermalinterface material applications has been developed and characterized. Both fabricationand metrology equipment has been developed for the purpose at hand. The composite isbased on a porous electrospun polymer carrier infiltrated with a high thermal conductivitymetal phase. The two phases form two fully interpenetrating networks in the composite.Efficient heat transfer is achieved through the continuous metal phase, while the polymericphase defines geometry and phase composition. The devised composite architecture is believedto be a step towards meeting current and future demands on thermal performanceand thermomechanical reliability in microelectronic products.Furthermore, the thesis presents initial results of human embryonic stem cell proliferationand neural differentiation in co-culture with electrospun scaffolds, of interestin future regenerative medicine based on stem cells. Results indicate that physical cuesemanating from cell-scaffold interactions affect cells towards a neuronal fate during differentiation,a phenomenon consistent with reports in literature on physical cues influencingstem cell fate. To allow for deeper analysis on cell-scaffold interactions of thetype described above, a microfabricated platform was developed for the purpose. A novelmethod for direct photolithographic micropatterning of electrospun polyurethane fibrousfilms over large surfaces has been devised. The method allows for assembly of complexelectrospun microstructures on single substrates via a multilayer approach involving multiplephotolithographic exposures, analogous to conventional photolithography in microfabricationof solid state devices. Indeed, this technique can find application in a variety ofapplications where it is beneficial to integrate micropatterned electrospun structures intomicrofabricated devices, in particular within biomedical engineering applications.
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| 4. |
- Jain, Saumey, et al.
(författare)
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On-Chip Neural Induction Boosts Neural Stem Cell Commitment : Toward a Pipeline for iPSC-Based Therapies
- 2024
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Ingår i: Advanced science (Weinheim, Baden-Wurttemberg, Germany). - : Wiley-VCH Verlagsgesellschaft. - 2198-3844.
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Tidskriftsartikel (refereegranskat)abstract
- The clinical translation of induced pluripotent stem cells (iPSCs) holds great potential for personalized therapeutics. However, one of the main obstacles is that the current workflow to generate iPSCs is expensive, time-consuming, and requires standardization. A simplified and cost-effective microfluidic approach is presented for reprogramming fibroblasts into iPSCs and their subsequent differentiation into neural stem cells (NSCs). This method exploits microphysiological technology, providing a 100-fold reduction in reagents for reprogramming and a ninefold reduction in number of input cells. The iPSCs generated from microfluidic reprogramming of fibroblasts show upregulation of pluripotency markers and downregulation of fibroblast markers, on par with those reprogrammed in standard well-conditions. The NSCs differentiated in microfluidic chips show upregulation of neuroectodermal markers (ZIC1, PAX6, SOX1), highlighting their propensity for nervous system development. Cells obtained on conventional well plates and microfluidic chips are compared for reprogramming and neural induction by bulk RNA sequencing. Pathway enrichment analysis of NSCs from chip showed neural stem cell development enrichment and boosted commitment to neural stem cell lineage in initial phases of neural induction, attributed to a confined environment in a microfluidic chip. This method provides a cost-effective pipeline to reprogram and differentiate iPSCs for therapeutics compliant with current good manufacturing practices.
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| 5. |
- Karlsson, Emma, 1983, et al.
(författare)
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In silico and in vitro studies of the reduction of unsaturated α,β bonds of trans-2-hexenedioic acid and 6-amino-trans-2-hexenoic acid – Important steps towards biobased production of adipic acid
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- The biobased production of adipic acid, a precursor in the production of nylon, is of great interest in order to replace the current petrochemical production route. Glucose-rich lignocel-lulosic raw materials have high potential to replace the petrochemical raw material. A number of metabolic pathways have been proposed for the microbial conversion of glucose to adipic acid, but achieved yields and titers remain to be improved before industrial applications are feasible. One proposed pathway starts with lysine, an essential metabolite industrially produced from glucose by microorganisms. However, the drawback of this pathway is that several reactions are involved where there is no known efficient enzyme. By changing the order of the enzymatic reactions, we were able to identify an alternative pathway with one unknown enzyme less compared to the original pathway. One of the reactions lacking known enzymes is the reduction of the unsaturated α,β bond of 6-amino-trans-2-hexenoic acid and trans-2hexenedioic acid. To identify the necessary enzymes, we selected N-ethylmaleimide reductase from Escherichia coli and Old Yellow Enzyme 1 from Saccharomyces pastorianus. Despite successful in silico docking studies, where both target substrates could fit in the enzyme pockets, and hydrogen bonds with catalytic residues of both enzymes were predicted, no in vitro activity was observed. We hypothesize that the lack of activity is due to a difference in electron withdrawing potential between the naturally reduced aldehyde and the carboxylate groups of our target substrates. Suggestions for protein engineering to induce the reactions are discussed, as well as the advantages and disadvantages of the two metabolic pathways from lysine. We have highlighted bottlenecks associated with the lysine pathways, and proposed ways of addressing them.
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| 6. |
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| 7. |
- Fu, Ying, 1964-, et al.
(författare)
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Endocytic pathway of vascular cell adhesion molecule 1 in human umbilical vein endothelial cell identified in vitro by using functionalized nontoxic fluorescent quantum dots
- 2019
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier B.V.. - 0925-4005 .- 1873-3077. ; 297
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Tidskriftsartikel (refereegranskat)abstract
- Studies about vascular cell adhesion molecule 1 (VCAM1) in tumor growth, metastasis, and angiogenesis suggest that targeting VCAM1 expression is an attractive strategy for diagnosis and anti-tumor therapy. However, the endocytic pathway of VCAM1 in vascular cells has not been well characterized. In this study we visualize the endocytic pathway of tumor necrosis factor α (TNFα) induced VCAM1 in human umbilical vein endothelial cell (HUVEC) in vitro using 5-carboxyfluorescein labeled VCAM1 binding peptides and fluorescent water-dispersible 3-mercaptopropionic acid (3MPA)-coated CdSe-CdS/Cd0.5Zn0.5S/ZnS core–multishell nontoxic quantum dots (3MPA-QDs) functionalized with VCAM1 binding peptides. Clear key in vitro observations are as follows: (a) 3MPA-QDs functionalized with VCAM1 binding peptides, denoted as VQDs, adhered and aggregated cumulatively to cell membrane around 2 h after VQD deposition to cell culture medium and were found in lysosomes in TNFα-treated HUVECs approximately 24 h after VQD deposition; (b) VQDs remained in TNFα-treated HUVECs for the whole 16 days of the experimental observation period; (c) quite differently, 3MPA-QDs were endocytosed then exocytosed by HUVECs via endosomes in about 24–48 h after 3MPA-QD deposition. Our study suggests that VCAM1 molecules, initially expressed on cell membrane induced by TNFα treatment, are internalized into lysosomes. This provides a novel means to deliver materials to lysosomes such as enzyme replacement therapy. Moreover, our meticulous sensing methodology of devising fluorescent nontoxic QDs advances biosensing technique for studying cellular activities in vitro and in vivo. © 2019 The Authors
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| 8. |
- Grandfield, Kathryn, 1986-, et al.
(författare)
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Ultrastructural characterisation of the hydroxyapatite–coated pedicle screw and human bone interface
- 2012
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Ingår i: International Journal of Nano and Biomaterials. - 1752-8933 .- 1752-8941. ; 4:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- The early fixation of pedicle screws is crucial for improving spinal stabilisation. Firm and immediate fixation between pedicle screws and bone prevents aseptic loosening and implant failure. Coating with hydroxyapatite is a possible method to improve the fixation of metallic implants in bone. In this study, scanning transmission electron microscopy (STEM) has been used to investigate the ultrastructure of the plasma–sprayed hydroxyapatite coating and human bone interface in detail. Focused ion beam sample preparation also enabled the investigation of the bone–lacunae interface. An intimate contact and elemental analysis between bone and HA coatings suggests bioactive fixation. Therefore, coating with hydroxyapatite leads to enhanced biocompatibility at the ultrastructural level and may lead to improved early and long–term fixation of pedicle screws.
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| 9. |
- Kmezik, Cathleen, 1991, et al.
(författare)
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Characterization of a novel multidomain CE15-GH8 enzyme encoded by a polysaccharide utilization locus in the human gut bacterium Bacteroides eggerthii
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Bacteroidetes are efficient degraders of complex carbohydrates, much thanks to their use of polysaccharide utilization loci (PULs). An integral part of PULs are highly specialized carbohydrate-active enzymes, sometimes composed of multiple linked domains with discrete functions—multicatalytic enzymes. We present the biochemical characterization of a multicatalytic enzyme from a large PUL encoded by the gut bacterium Bacteroides eggerthii . The enzyme, Be CE15A-Rex8A, has a rare and novel architecture, with an N-terminal carbohydrate esterase family 15 (CE15) domain and a C-terminal glycoside hydrolase family 8 (GH8) domain. The CE15 domain was identified as a glucuronoyl esterase (GE), though with relatively poor activity on GE model substrates, attributed to key amino acid substitutions in the active site compared to previously studied GEs. The GH8 domain was shown to be a reducing-end xylose-releasing exo-oligoxylanase (Rex), based on having activity on xylooligosaccharides but not on longer xylan chains. The full-length Be CE15A-Rex8A enzyme and the Rex domain were capable of boosting the activity of a commercially available GH11 xylanase on corn cob biomass. Our research adds to the understanding of multicatalytic enzyme architectures and showcases the potential of discovering novel and atypical carbohydrate-active enzymes from mining PULs.
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| 10. |
- Munthe, Christian, 1962
(författare)
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The Price of Precaution and the Ethics of Risk
- 2011
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Since a couple of decades, the notion of a precautionary principle plays a central and increasingly influential role in international as well as national policy and regulation regarding the environment and the use of technology. Urging society to take action in the face of potential risks of human activities in these areas, the recent focus on climate change has further sharpened the importance of this idea. However, the idea of a precautionary principle has also been problematised and criticised by scientists, scholars and policy activists, and been accused of almost every intellectual sin imaginable: unclarity, impracticality, arbitrariness and moral as well as political unsoundness. In that light, the very idea of precaution as an ideal for policy making rather comes out as a dead end. On the basis of these contrasting starting points, Christian Munthe undertakes an innovative, in-depth philosophical analysis of what the idea of a precautionary principle is and should be about. A novel theory of the ethics of imposing risks is developed and used as a foundation for defending the idea of precaution in environmental and technological policy making against its critics, while at the same time avoiding a number of identified flaws. The theory is shown to have far-reaching consequences for areas such as bio-, information- and nuclear technology, and global environmental policy in areas such as climate change. The author argues that, while the price we pay for precaution must not be too high, we have to be prepared to pay it in order to act ethically defensible. A number of practical suggestions for precautionary regulation and policy making are made on the basis of this, and some challenges to basic ethical theory as well as consumerist societies, the global political order and liberal democracy are identified
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