| 1. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 2. |
- Matthiesen, Isabelle, et al.
(författare)
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Continuous Monitoring Reveals Protective Effects of N‐Acetylcysteine Amide on an Isogenic Microphysiological Model of the Neurovascular Unit
- 2021
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 17:32, s. 2101785-
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Tidskriftsartikel (refereegranskat)abstract
- Microphysiological systems mimic the in vivo cellular ensemble and microenvironment with the goal of providing more human-like models for biopharmaceutical research. In this study, the first such model of the blood-brain barrier (BBB-on-chip) featuring both isogenic human induced pluripotent stem cell (hiPSC)-derived cells and continuous barrier integrity monitoring with <2 min temporal resolution is reported. Its capabilities are showcased in the first microphysiological study of nitrosative stress and antioxidant prophylaxis. Relying on off-stoichiometry thiol–ene–epoxy (OSTE+) for fabrication greatly facilitates assembly and sensor integration compared to the prevalent polydimethylsiloxane devices. The integrated cell–substrate endothelial resistance monitoring allows for capturing the formation and breakdown of the BBB model, which consists of cocultured hiPSC-derived endothelial-like and astrocyte-like cells. Clear cellular disruption is observed when exposing the BBB-on-chip to the nitrosative stressor linsidomine, and the barrier permeability and barrier-protective effects of the antioxidant N-acetylcysteine amide are reported. Using metabolomic network analysis reveals further drug-induced changes consistent with prior literature regarding, e.g., cysteine and glutathione involvement. A model like this opens new possibilities for drug screening studies and personalized medicine, relying solely on isogenic human-derived cells and providing high-resolution temporal readouts that can help in pharmacodynamic studies.
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| 3. |
- Trigo, João Pedro, 1995, et al.
(författare)
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In vitro digestibility and Caco-2 cell bioavailability of sea lettuce (Ulva fenestrata) proteins extracted using pH-shift processing
- 2021
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- Seaweed is a promising sustainable source of vegan protein as its farming does not require arable land, pesticides/insecticides, nor freshwater supply. However, to be explored as a novel protein source the content and nutritional quality of protein in seaweed need to be improved. We assessed the influence of pH-shift processing on protein degree of hydrolysis (%DH), protein/peptide size distribution, accessibility, and cell bioavailability of Ulva fenestrata proteins after in vitro gastrointestinal digestion. pH-shift processing of Ulva, which concentrated its proteins 3.5-times, significantly improved the %DH from 27.7±2.6% to 35.7±2.1% and the amino acid accessibility from 56.9±4.1% to 72.7±0.6%. Due to the higher amino acid accessibility, the amount of most amino acids transported across the cell monolayers was higher in the protein extracts. Regarding bioavailability, both Ulva and protein extracts were as bioavailable as casein. The protein/peptide molecular size distribution after digestion did not disclose a clear association with bioavailability.
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| 4. |
- Bondesson, Johan, 1991
(författare)
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Geometric Modeling of Thoracic Aortic Surface Morphology - Implications for Pathophysiology and Clinical Interventions
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vascular disease risk factors such as hypertension, hyperlipidemia and old age are all results of modern-day lifestyle, and these diseases are getting more and more common. One treatment option for vascular diseases such as aneurysms and dissections is endovascular aortic repair introduced in the early 1990s. This treatment uses tubular fabric covered metallic structures (endografts) that are implanted using a minimally invasive approach and placed to serve as an articial vessel in a damaged portion of the vasculature. To ensure that the interventions are successful, the endograft must be placed in the correct location, and designed to sustain the hostile biological, chemical, and mechanical conditions in the body for many years. This is an interaction that goes both ways, and keeping in mind that the endograft is a foreign object placed in the sensitive vascular system, it is also important that it does not disrupt the native conditions more than necessary. This thesis presents a segmentation and quantication methodology to accurately describe the complex morphology and motion of diseased blood vessels in vivo through a natural and intuitive description of their luminal surfaces. After methodology validation, a series of important clinical applications are performed, all based on non-invasive imaging. Firstly, it is shown that explicit surface curvature quantication is necessary when compared to relying solely on centerline curvature and estimation methods. Secondly, it is shown that endograft malapposition severity can be predicted from preoperative geometric analysis of thoracic aortic surfaces. Thirdly, a multiaxial dynamics analysis of cardiac induced thoracic aortic surface motion shows how thoracic endovascular aortic repair affects the deformations of the dierent portions of the thoracic aorta. Fourthly, the helical propagation pattern of type B aortic dissection is determined, and two distinct modes of chirality are revealed, i.e., achiral and right-handed chiral groups. Finally, the effects of thoracic endovascular aortic repair on helical and cross-sectional morphology of type B dissections are investigated revealing how acuity and chirality affects the alteration due to intraluminal lining with endografts. Thus, the work presented in this thesis contributes by adding knowledge about pathology and pathophysiology through better geometric description of surface conditions of diseased thoracic aortas. This gives clinicians insights to use in their treatment planning and provides more nuanced boundary conditions for endograft manufacturers. Comprehensive knowledge about diseases, better treatment planning, and better devices are all crucial in order to improve the outcomes of performed interventions and ultimately the quality of life for the treated patients.
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| 5. |
- Beiranvand, B., et al.
(författare)
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A distributed terahertz metasurface with cold-electron bolometers for cosmology missions
- 2021
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Ingår i: Applied Sciences (Switzerland). - : MDPI AG. - 2076-3417. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- We developed and tested a 2D periodic array of cold-electron bolometers arranged into a wideband frequency selective metasurface that absorbs more than 70% of the incident power in the frequency range 100–800 GHz. The array had 10 × 10 unit cells, each containing four bolometers incorporated into a ring. The chip with bolometers was mounted on the back side of the silicon lens without a back-reflector. Preliminary experiments demonstrated voltage responsivity as high as 10 V/W for the current-biased series array. Simulation of the noise performance shows realization of background noise-limited performance with NEP < NEP for the optical power load P > 15 pW. Results of numerical simulation made for the unit cell of the array are presented together with the equivalent diagram based on lumped network elements. The unit cell also was developed numerically to operate in two radiation modes.
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| 6. |
- Khatun, Ayesha, et al.
(författare)
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University College London/University of Gothenburg PhD course "Biomarkers in neurodegenerative diseases" 2019-course organisation.
- 2020
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- Biomarkers are increasingly employed for effective research into neurodegenerative diseases. They have become essential for reaching an accurate clinical diagnosis, monitoring disease, and refining entry criteria for participation in clinical treatment trials, and will be key in measuring target engagement and treatment outcome in disease-modifying therapies. Emerging techniques and research combining different biomarker modalities continue to strengthen our understanding of the underlying pathology and the sequence of pathogenic events. Given recent advances, we are now at a pivotal stage in biomarker research. PhD students working in the field of neurodegenerative disease require a working knowledge of a range of biomarkers available and their limitations, to correctly interpret scientific literature and to design and conduct successful research studies themselves. Here, we outline the University College London/University of Gothenburg "Biomarkers in neurodegenerative diseases course", the first initiative of its kind aimed to bring together both experts and PhD students from all areas within the field of neurodegeneration, to provide comprehensive knowledge of biomarker research for the next generation of scientists.
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| 7. |
- 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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| 8. |
- Walladbegi, Java, et al.
(författare)
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Three-dimensional bioprinting using a coaxial needle with viscous inks in bone tissue engineering - An in vitro study
- 2020
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Ingår i: Annals of Maxillofacial Surgery. - : Medknow. - 2249-3816 .- 2231-0746. ; 10:2, s. 370-376
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Vascularized autologous tissue grafts are considered 'gold standard' for the management of larger bony defects in the craniomaxillofacial area. This modality does however carry limitations, such as the absolute requirement for healthy donor tissues and recipient vessels. In addition, the significant morbidity of large bone graft is deterrent to fibula bone flap use. Therefore, less morbid strategies would be beneficial. The purpose of this study was to develop a printing method to manufacture scaffold structure with viable stem cells. Materials and Methods: In total, three different combinations of ground beta tri-calcium phosphate and CELLINK (bioinks) were printed with a nozzle to identify a suitable bioink for three-dimensional printing. Subsequently, a coaxial needle, with three different nozzle gauge combinations, was evaluated for printing of the bioinks. Scaffold structures (grids) were then printed alone and with additional adipose stem cells before being transferred into an active medium and incubated overnight. Following incubation, grid stability was evaluated by assessing the degree of maintained grid outline, and cell viability was determined using the live/dead cell assay. Results: Among the three evaluated combinations of bioinks, two resulted in good printability for bioprinting. Adequate printing was obtained with two out of the three nozzle gauge combinations tested. However, due to the smaller total opening, one combination revealed a better stability. Intact grids with maintained stability were obtained using Ink B23 and Ink B42, and approximately 80% of the printed stem cells were viable following 24 hours. Discussion: Using a coaxial needle enables printing of a stable scaffold with viable stem cells. Furthermore, cell viability is maintained after the bioprinting process.
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| 9. |
- Nilsson, Avlant, 1985, et al.
(författare)
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Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:19, s. 10294-10304
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Tidskriftsartikel (refereegranskat)abstract
- Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.
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| 10. |
- Sun, He
(författare)
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Antibiotic resistance in biogas processes
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anaerobic digestion (AD) is a well-established technology that can play a key role in development of a sustainable society. In AD, organic wastes such as animal manure, food waste and crop residues are used as substrate and converted to biogas and digestate, which represent green energy and a biofertiliser. Due to intensive use of veterinary antibiotics, antibiotic residues, antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) enter the AD process via the substrates and end up in the digestate. Thus, digestate may represent a source of spread of antibiotic resistance. Antibiotic resistance is one of the greatest global public health challenges of our time and is predicted to cause around 300 million premature deaths by 2050, so countering its spread is critically important. However, research on the antibiotic resistance level in AD is still quite limited. This thesis contributed essential new knowledge by a) identifying ARB communities in digestates originating from food waste, crops and dairy manure; b) assessing antibiotic resistance in plant-based substrates; c) investigating phenotypic and genotypic resistance pattern and resistance transferability of isolated ARB; and d) comparing molecular and culture-dependent methods in evaluation of antibiotic resistance. Bacillus and closely-related genera such as Paenibacillus and Lysinibacillus were found to dominate the ARB community isolated from digestate, irrespective of substrate type. Most ARGs identified for these ARB were located on chromosomes, although several ARB strains had extra-chromosomal genomes. Only one was identified as a plasmid (pAMαl), which proved to be nontransferable in plasmid conjugation testing. Thus, the dominant ARB community from the digestates studied likely poses a limited risk of antibiotic resistance spread, although even plant-based substrates were found to contain variant antibiotic resistance components. Combined use of molecular and culturedependent methods was required to reveal the true antibiotic resistance situation in the AD process.
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