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| 2. |
- 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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| 3. |
- 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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| 4. |
- Enroth, Stefan, et al.
(författare)
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Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations
- 2016
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 12, s. 309-314
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Tidskriftsartikel (refereegranskat)abstract
- The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.
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| 5. |
- 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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| 6. |
- Rasmusson, Lars, 1962, et al.
(författare)
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Autogena stamceller för benrekonstruktion av defekter i käkarna
- 2018
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Ingår i: Tandläkartidningen. - 0039-6982. ; 109:11, s. 104-108
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Tidskriftsartikel (refereegranskat)abstract
- Fallbeskrivning av 2 patienter som efter misslyckad rekonstruktion av underkäken med autologa bentransplantat rekonstruerades med ben utvunnet ur stamceller från patientens egen fettvävnad. Differentiering och cellvitalitet kunde bekräftas före re-implantation. Moget ben kunde konstateras kliniskt, histologiskt och radiologiskt efter 1 år.
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| 7. |
- Klintberg, Anton, 1989, et al.
(författare)
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Kalman filter for adaptive learning of two-dimensional look-up tables applied to OCV-curves for aged battery cells
- 2019
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Ingår i: Control Engineering Practice. - : Elsevier BV. - 0967-0661. ; 84, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- In online automotive applications it is common to use look-up tables, or maps, to describe nonlinearities in component models that are to be valid over large operating ranges. If the component characteristics change with aging or wear, these look-up tables must be updated online. For 2-D look-up tables, the existing methods in the literature only adapt the observable parameters in the look-up table, which means that parameters in operation points that have not been visited for a long time may be far from their true values. In this work, correlations between different operating points are used to also update non-observable parameters of the look-up table. The method is applied to Open Circuit Voltage (OCV) curves for aged battery cells. From laboratory experimental data it is demonstrated that the proposed method can significantly reduce the average deviation from an aged OCV-curve compared to keeping the OCV-curve from the beginning of the cell's life, both for observable and non-observable parameters.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Zhdanov, Vladimir, 1952
(författare)
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Spatio-temporal aspects of the interplay of cancer and the immune system
- 2019
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Ingår i: Journal of Biological Physics. - : Springer Science and Business Media LLC. - 0092-0606 .- 1573-0689. ; 45:4, s. 395-400
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Tidskriftsartikel (refereegranskat)abstract
- The conventional mean-field kinetic models describing the interplay of cancer and the immune system are temporal and predict exponential growth or elimination of the population of tumour cells provided their number is small and their effect on the immune system is negligible. More complex kinetics are associated with non-linear features of the response of the immune system. The generic model presented in this communication takes into account that the rates of the birth and death of tumour cells inside a tumour spheroid can significantly depend on the radial coordinate due to diffusion limitations in the supply of nutrients and/or transport of the species (cells and proteins) belonging to the immune system. In this case, non-trivial kinetic regimes are shown to be possible even without appreciable perturbation of the immune system.
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