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- Gunnarson, Eli, et al.
(författare)
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Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection.
- 2009
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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. - 1091-6490. ; 106:5, s. 1602-7
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Tidskriftsartikel (refereegranskat)abstract
- Disturbed brain water homeostasis with swelling of astroglial cells is a common complication in stroke, trauma, and meningitis and is considered to be a major cause of permanent brain damage. Astroglial cells possess the water channel aquaporin 4 (AQP4). Recent studies from our laboratory have shown that glutamate, acting on group I metabotropic glutamate receptors (mGluRs), increases the permeability of astrocyte AQP4, which, in situations of hypoxia-ischemia, will increase astrocyte water uptake. Here we report that erythropoietin (EPO), which in recent years has emerged as a potent neuro-protective agent, antagonizes the effect of a group I mGluR agonist on astrocyte water permeability. Activation of group I mGluRs triggers fast and highly regular intracellular calcium oscillations and we show that EPO interferes with this signaling event by altering the frequency of the oscillations. These effects of EPO are immediate, in contrast to the neuroprotective effects of EPO that are known to depend upon gene activation. Our findings indicate that EPO may directly reduce the risk of astrocyte swelling in stroke and other brain insults. In support of this conclusion we found that EPO reduced the neurological symptoms in a mouse model of primary brain edema known to depend upon AQP4 water transport.
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- Khorshidi, Mohammad Ali, et al.
(författare)
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Analysis of transient migration behavior of natural killer cells imaged in situ and in vitro
- 2011
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Ingår i: Integrative Biology. - : Oxford University Press (OUP). - 1757-9694 .- 1757-9708. ; 3:7, s. 770-778
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Tidskriftsartikel (refereegranskat)abstract
- We present a simple method for rapid and automatic characterization of lymphocyte migration from time-lapse fluorescence microscopy data. Time-lapse imaging of natural killer (NK) cells in vitro and in situ, both showed that individual cells transiently alter their migration behavior. Typically, NK cells showed periods of high motility, interrupted by transient periods of slow migration or almost complete arrests. Analysis of in vitro data showed that these periods frequently coincided with contacts with target cells, sometimes leading to target cell lysis. However, NK cells were also commonly observed to stop independently of contact with other cells. In order to objectively characterize the migration of NK cells, we implemented a simple method to discriminate when NK cells stop or have low motilities, have periods of directed migration or undergo random movement. This was achieved using a sliding window approach and evaluating the mean squared displacement (MSD) to assess the migration coefficient and MSD curvature along trajectories from individual NK cells over time. The method presented here can be used to quickly and quantitatively assess the dynamics of individual cells as well as heterogeneity within ensembles. Furthermore, it may also be used as a tool to automatically detect transient stops due to the formation of immune synapses, cell division or cell death. We show that this could be particularly useful for analysis of in situ time-lapse fluorescence imaging data where most cells, as well as the extracellular matrix, are usually unlabelled and thus invisible.
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| 8. |
- Kowalewski, Jacob M., et al.
(författare)
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Generation of Slow Calcium oscillations in Spatial Cell Models Driven by Store Operated Calcium Entry
- 2004
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Konferensbidrag (refereegranskat)abstract
- Calcium signaling is involved in many cellular processes ranging from fertilization to apoptosis. We have created two general mathematical models to simulate calcium transport between the endoplasmic reticulum (ER), the cytosol and the extracellular environment. Active in this process is inositol-1,4,5-trisphosphate (InsP3). The behavior of the changes in calcium concentration was studied. The first model is compartmental and uses ordinary differential equations. The second one is a spatial model, which uses partial differential equations. The tools used in constructing these models were MATLAB and Virtual Cell. Store operated calcium entry can be observed in experiments with living cells when the sarco(endo)plasmic reticulum calcium-ATPase (SERCA) pumps are blocked by cyclopiazonic acid (CPA) or thapsigargin. We have developed a phenomenological model of store operated calcium channels (SOC). This model involves a diffusible messenger that leaves the ER and binds to a channel in the plasma membrane. Many parameters in the models are not fully known. A basic assumption is that the parameters can be estimated from the fact that a cell at rest has an almost constant level of calcium. Results from both the compartmental and the spatial simulations show that InsP3 can cause the cytosolic calcium level to oscillate at frequencies between 1 and 5 mHz. Experimental studies have shown than calcium oscillations in this frequency range are present in renal cells. The SERCA blocking simulations show good similarity with experimental results. The results also show that the high surface-to-volume ratio of the ER is important for causing oscillations.
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| 9. |
- Kowalewski, Jacob M, et al.
(författare)
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Modeling the impact of store-operated Ca2+ entry on intracellular Ca2+ oscillations
- 2006
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Ingår i: Mathematical biosciences. - : Elsevier BV. - 0025-5564. ; 204:2, s. 232-249
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Tidskriftsartikel (refereegranskat)abstract
- Calcium (Ca2+) oscillations play fundamental roles in various cell signaling processes and have been the subject of numerous modeling studies. Here we have implemented a general mathematical model to simulate the impact of store-operated Ca2+ entry on intracellular Ca2+ oscillations. In addition, we have compared two different models of the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and their influences on intracellular Ca2+ oscillations. Store-operated Ca2+ entry following Ca2+ depletion of endoplasmic reticulum (ER) is an important component of Ca2+ signaling. We have developed a phenomenological model of store-operated Ca2+ entry via store-operated Ca2+ (SOC) channels, which are activated upon ER Ca2+ depletion. The depletion evokes a bi-phasic Ca2+ signal, which is also produced in our mathematical model. The IP3R is an important regulator of intracellular Ca2+ signals. This IP3 sensitive Ca2+ channel is also regulated by Ca2+. We apply two IP3R models, the Mak-McBride-Foskett model and the De Young and Keizer model, with significantly different channel characteristics. Our results show that the two separate IP3R models evoke intracellular Ca2+ oscillations with different frequencies and amplitudes. Store-operated Ca2+ entry affects the oscillatory behavior of these intracellular Ca2+ oscillations. The IP3 threshold is altered when store-operated Ca2+ entry is excluded from the model. Frequencies and amplitudes of intracellular Ca2+ oscillations are also altered without store-operated Ca2+ entry. Under certain conditions, when intracellular Ca2+ oscillations are absent, excluding store-operated Ca2+ entry induces an oscillatory response. These findings increase knowledge concerning store-operated Ca2+ entry and its impact on intracellular Ca2+ oscillations.
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- Rydholm, Susanna, et al.
(författare)
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Microfluidic devices for studies of primary cilium mediated cellular response to dynamic flow conditions
- 2008
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Ingår i: Biomedical microdevices (Print). - : Springer Science and Business Media LLC. - 1387-2176 .- 1572-8781. ; 10:4, s. 555-560
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Tidskriftsartikel (refereegranskat)abstract
- We present the first microfabricated microfluidic devices designed specifically for studies of primary cilium mediated cellular response to dynamic flow. The primary cilium functions as a mechano-sensor in renal tubular epithelium, sensing the extracellular fluid flow. Malfunction of cilia has been implicated in e.g. polycystic kidney disease and other pathological conditions. Bending of the primary cilium by fluid flow has been shown to give rise to an intracellular calcium signal, however little is known about the sensitivity to flow duration, magnitude and direction. This paper presents a novel method for studying cilia forming cells in asymmetric microfluidic environments. The microfluidic devices presented here were designed for a dynamic control of the local fluid flow on a cellular level, and thus, enables studies of cellular responses to an amplitude, frequency and direction controlled cilium movement.
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