| 1. |
- 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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| 2. |
- Padra, János T, et al.
(författare)
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Optimization of Alcian blue pH1.0 histo-staining protocols to match mass spectrometric quantification of sulfomucins and circumvent false positive results due to sialomucins.
- 2022
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 32:1, s. 6-10
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Tidskriftsartikel (refereegranskat)abstract
- Sulfomucins are in some body-locations and species a normal occurrence, whereas in other situations a sign of pathology. Sulfomucin content on histological sections and isolated material is frequently analyzed with Alcian blue staining at pH1.0. However, since the stain detects the charge, a high density of other charged molecules, such as sialic acids has potential to impede specificity. Here, we compared the outcome from four staining protocols with the level of sulfation determined by liquid chromatography-tandem mass spectrometry analysis (MS) on samples from various tissues with variable sulfation and sialylation levels. We found that a protocol we designed, including rinsing with MetOH and 0.5M NaCl buffer at pH1.0 eliminates false positive staining of tissues outperforming commonly recommended solutions. In tissues with low to moderately sulfated mucins (e.g. human stomach and salmonid epithelia) this method enables accurate relative quantification (e.g. sulfate scoring comparisons between healthy and diseased tissues) whereas the range of the method is not suitable for comparisons between tissues with high sulfomucin content (e.g. pig stomach and colon).
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| 3. |
- 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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| 4. |
- Micheletti, Chiara, et al.
(författare)
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Ultrastructure and Nanoporosity of Human Bone Shown with Correlative On-Axis Electron and Spectroscopic Tomographies
- 2023
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Ingår i: ACS Nano. - 1936-0851 .- 1936-086X. ; 17:24, s. 24710-24724
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Tidskriftsartikel (refereegranskat)abstract
- Mineralized collagen fibrils are the building block units of bone at the nanoscale. While it is known that collagen fibrils are mineralized both inside their gap zones (intra-fibrillar mineralization) and on their outer surfaces (extra-fibrillar mineralization), a clear visualization of this architecture in three dimensions (3D), combining structural and compositional information over large volumes, but without compromising the resolution, remains challenging. In this study, we demonstrate the use of on-axis Z-contrast electron tomography (ET) with correlative energy-dispersive X-ray spectroscopy (EDX) tomography to examine rod-shaped samples with diameters up to 700 nm prepared from individual osteonal lamellae in the human femur. Our work mainly focuses on two aspects: (i) low-contrast nanosized circular spaces (“holes”) observed in sections of bone oriented perpendicular to the long axis of a long bone, and (ii) extra-fibrillar mineral, especially in terms of morphology and spatial relationship with respect to intra-fibrillar mineral and collagen fibrils. From our analyses, it emerges quite clearly that most “holes” are cross-sectional views of collagen fibrils. While this had been postulated before, our 3D reconstructions and reslicing along meaningful two-dimensional (2D) cross-sections provide a direct visual confirmation. Extra-fibrillar mineral appears to be composed of thin plates that are interconnected and span over several collagen fibrils, confirming that mineralization is cross-fibrillar, at least for the extra-fibrillar phase. EDX tomography shows mineral signatures (Ca and P) within the gap zones, but the signal appears weaker than that associated with the extra-fibrillar mineral, pointing toward the existence of dissimilarities between the two types of mineralization.
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| 5. |
- Pless, Christian J., et al.
(författare)
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Emerging strategies in 3D printed tissue models for in vitro biomedical research
- 2022
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Ingår i: Bioprinting : From Multidisciplinary Design to Emerging Opportunities - From Multidisciplinary Design to Emerging Opportunities. - 9780323854306 - 9780323854313 ; , s. 207-246
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Bokkapitel (refereegranskat)abstract
- 3D bioprinting has the potential to provide a unified framework for the manufacturing of tissue models for biomedical research, including drug discovery, disease modeling, and regenerative medicine. However, it remains challenging to 3D print replicas of human tissues that have accurate cell types, cellular densities, extracellular matrix compositions, and that can be assayed in a minimally invasive manner for chronic studies. Here, we review how recent breakthroughs in stem cell biology, tissue engineering, and materials science have led to novel 3D printing strategies that have the potential to solve these challenges.
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| 6. |
- Elson, Frank, et al.
(författare)
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TRIM Simulations Tool for μ + Stopping Fraction in Hydrostatic Pressure Cells
- 2023
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 2462:1
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Konferensbidrag (refereegranskat)abstract
- For quantum systems or materials, a common procedure for probing their behaviour is to tune electronic/magnetic properties using external parameters, e.g. temperature, magnetic field or pressure. Pressure application as an external stimuli is a widely used tool, where the sample in question is inserted into a pressure cell providing a hydrostatic pressure condition. Such device causes some practical problems when using in Muon Spin Rotation/Relaxation (μ +SR) experiments as a large proportion of the muons will be implanted in the pressure cell rather than in the sample, resulting in a higher background signal. This issue gets further amplified when the temperature dependent response from the sample is much smaller than that of the pressure cell,which may cause the sample response to be lost in the background and cause difficulties in aligning the sample within the beam. To tackle this issue, we have used pySRIM [1] to construct a practical and helpful simulation tool for calculating muon stopping fractions, specifically for the pressure cell setup at the μE1 beamline using the GPD spectrometer at the Paul Scherrer Institute, with the use of TRIM simulations. The program is used to estimate the number of muon stopping in both the sample and the pressure cell at a given momentum. The simultion tool is programmed into a GUI, making it accessible to user to approximate prior to their experiments at GPD what fractions will belong to the sample and the pressure cell in their fitting procedure.
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| 7. |
- Rosén, Emil, et al.
(författare)
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Inference of glioblastoma migration and proliferation rates using single time-point images
- 2023
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Cancer cell migration is a driving mechanism of invasion in solid malignant tumors. Anti-migratory treatments provide an alternative approach for managing disease progression. However, we currently lack scalable screening methods for identifying novel anti-migratory drugs. To this end, we develop a method that can estimate cell motility from single end-point images in vitro by estimating differences in the spatial distribution of cells and inferring proliferation and diffusion parameters using agent-based modeling and approximate Bayesian computation. To test the power of our method, we use it to investigate drug responses in a collection of 41 patient-derived glioblastoma cell cultures, identifying migration-associated pathways and drugs with potent anti-migratory effects. We validate our method and result in both in silico and in vitro using time-lapse imaging. Our proposed method applies to standard drug screen experiments, with no change needed, and emerges as a scalable approach to screen for anti-migratory drugs. The spatial positioning of cultured glioblastoma cells is used to estimate cell motility and drug effects from single end-point images in vitro.
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| 8. |
- Trossbach, Martin, et al.
(författare)
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A Portable, Negative-Pressure Actuated, Dynamically Tunable Microfluidic Droplet Generator
- 2022
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Ingår i: Micromachines. - : MDPI AG. - 2072-666X. ; 13:11, s. 1823-1823
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Tidskriftsartikel (refereegranskat)abstract
- Droplet microfluidics utilize a monodisperse water-in-oil emulsion, with an expanding toolbox offering a wide variety of operations on a range of droplet sizes at high throughput. However, translation of these capabilities into applications for non-expert laboratories to fully harness the inherent potential of microscale manipulations is woefully trailing behind. One major obstacle is that droplet microfluidic setups often rely on custom fabricated devices, costly liquid actuators, and are not easily set up and operated by non-specialists. This impedes wider adoption of droplet technologies in, e.g., the life sciences. Here, we demonstrate an easy-to-use minimal droplet production setup with a small footprint, built exclusively from inexpensive commercially sourced parts, powered and controlled by a laptop. We characterize the components of the system and demonstrate production of droplets ranging in volume from 3 to 21 nL in a single microfluidic device. Furthermore, we describe the dynamic tuning of droplet composition. Finally, we demonstrate the production of droplet-templated cell spheroids from primary cells, where the mobility and simplicity of the setup enables its use within a biosafety cabinet. Taken together, we believe this minimal droplet setup is ideal to drive broad adoption of droplet microfluidics technology.
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| 9. |
- Abdul-Jabbar, Thealfaqar A., et al.
(författare)
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Efficient Battery Cell Balancing Methods for Low-Voltage Applications: A Review
- 2022
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Ingår i: 2022 IEEE International Conference in Power Engineering Application, ICPEA 2022 - Proceedings.
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Konferensbidrag (refereegranskat)abstract
- Battery balancing technologies are a crucial mech anism for the safe operation of electrochemical energy storage systems, such as lithium-ion batteries. Moreover, balancing be tween battery cells is essential for battery systems' life. Without any balancing circuitry, individual cell voltages can reach their maximum/minimum battery voltage limit faster than others, posing safety hazards. Furthermore, battery capacity reduction can occur when overcharging/over-discharging individual cells. So far, many balancing methodologies have been proposed and discussed in available literature. This paper presents a review of different state-of-The-Art cell balancing methods suitable for low voltage applications. The required control complexity, switch stress, balancing speed, cost and circuit size are considered as key aspects. Typically, cell bypass techniques, such as passive balancing, have the lowest cost and require no complex control strategies. In contrast, cell-To-cell balancing techniques can significantly increase the energy efficiency compared to cell bypass balancers, but these come with higher system costs and control complexity.
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| 10. |
- Ahkami, Bahareh, et al.
(författare)
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Electromyography-Based Control of Lower Limb Prostheses: A Systematic Review
- 2023
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Ingår i: IEEE Transactions on Medical Robotics and Bionics. - 2576-3202. ; 5:3, s. 547-562
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Tidskriftsartikel (refereegranskat)abstract
- Most amputations occur in lower limbs and despite improvements in prosthetic technology, no commercially available prosthetic leg uses electromyography (EMG) information as an input for control. Efforts to integrate EMG signals as part of the control strategy have increased in the last decade. In this systematic review, we summarize the research in the field of lower limb prosthetic control using EMG. Four different online databases were searched until June 2022: Web of Science, Scopus, PubMed, and Science Direct. We included articles that reported systems for controlling a prosthetic leg (with an ankle and/or knee actuator) by decoding gait intent using EMG signals alone or in combination with other sensors. A total of 1,331 papers were initially assessed and 121 were finally included in this systematic review. The literature showed that despite the burgeoning interest in research, controlling a leg prosthesis using EMG signals remains challenging. Specifically, regarding EMG signal quality and stability, electrode placement, prosthetic hardware, and control algorithms, all of which need to be more robust for everyday use. In the studies that were investigated, large variations were found between the control methodologies, type of research participant, recording protocols, assessments, and prosthetic hardware.
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