| 1. |
- Vizlin-Hodzic, Dzeneta, et al.
(författare)
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Early onset of inflammation during ontogeny of bipolar disorder: the NLRP2 inflammasome gene distinctly differentiates between patients and healthy controls in the transition between iPS cell and neural stem cell stages
- 2017
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Neuro-inflammation and neuronal communication are considered as mis-regulated processes in the aetiology and pathology of bipolar disorder (BD). Which and when specific signal pathways become abnormal during the ontogeny of bipolar disorder patients is unknown. To address this question, we applied induced pluripotent stem cell (iPSC) technology followed by cortical neural differentiation on adipocyte-derived cells from BD type I patients (with psychotic episodes in psychiatric history) and healthy volunteers (controls). RNA sequencing in iPSC and cortical neural stem cell (NSC) lines were used to examine alterations between the transcriptomes from BD I and control samples during transition from the pluripotent stage towards the neural developmental stage. At the iPSC stage, the most highly significant differentially expressed gene (DEG) was the NLRP2 inflammasome (P = 2.66 × 10-10). Also among 42 DEGs at the NSC stage, NLRP2 showed the strongest statistical significance (P = 3.07 × 10-19). In addition, we have also identified several cytoskeleton-associated genes as DEGs from the NSC stage, such as TMP2, TAGLN, and ACTA2; the former two genes are recognised for the first time to be associated with BD. Our results also suggest that iPSC-derived BD-cortical NSCs carry several abnormalities in dopamine and GABA receptor canonical pathways, underlining that our in vitro BD model reflects pathology in the CNS. This would indicate that mis-regulated gene expression of inflammatory, neurotransmitter, and cytoskeletal signalling occurs during early foetal brain development of BD I patients.
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| 2. |
- Wallén-Mackenzie, Åsa, et al.
(författare)
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Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function.
- 2009
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401 .- 0270-6474. ; 29:7, s. 2238-51
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in neuroscience is to resolve the connection between gene functionality, neuronal circuits, and behavior. Most, if not all, neuronal circuits of the adult brain contain a glutamatergic component, the nature of which has been difficult to assess because of the vast cellular abundance of glutamate. In this study, we wanted to determine the role of a restricted subpopulation of glutamatergic neurons within the forebrain, the Vglut2-expressing neurons, in neuronal circuitry of higher brain function. Vglut2 expression was selectively deleted in the cortex, hippocampus, and amygdala of preadolescent mice, which resulted in increased locomotor activity, altered social dominance and risk assessment, decreased sensorimotor gating, and impaired long-term spatial memory. Presynaptic VGLUT2-positive terminals were lost in the cortex, striatum, nucleus accumbens, and hippocampus, and a downstream effect on dopamine binding site availability in the striatum was evident. A connection between the induced late-onset, chronic reduction of glutamatergic neurotransmission and dopamine signaling within the circuitry was further substantiated by a partial attenuation of the deficits in sensorimotor gating by the dopamine-stabilizing antipsychotic drug aripiprazole and an increased sensitivity to amphetamine. Somewhat surprisingly, given the restricted expression of Vglut2 in regions responsible for higher brain function, our analyses show that VGLUT2-mediated neurotransmission is required for certain aspects of cognitive, emotional, and social behavior. The present study provides support for the existence of a neurocircuitry that connects changes in VGLUT2-mediated neurotransmission to alterations in the dopaminergic system with schizophrenia-like behavioral deficits as a major outcome.
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| 3. |
- Bergström, Petra, et al.
(författare)
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Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) and its cleavage product amyloid beta (A beta) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. alpha-Cleaved soluble APP (sAPP alpha) was secreted early during differentiation, from neuronal progenitors, while beta-cleaved soluble APP (sAPP beta) was first secreted after deep-layer neurons had formed. Short A beta peptides, including A beta 1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as A beta 1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by A beta 1-40/42, is associated with mature neuronal phenotypes.
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| 4. |
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| 5. |
- Faijerson, Jonas, 1977, et al.
(författare)
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Adult neural stem/progenitor cells reduce NMDA-induced excitotoxicity via the novel neuroprotective peptide pentinin.
- 2009
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Ingår i: Journal of neurochemistry. - 1471-4159. ; 109:3, s. 858-66
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Tidskriftsartikel (refereegranskat)abstract
- Although the potential of adult neural stem cells to repair damage via cell replacement has been widely reported, the ability of endogenous stem cells to positively modulate damage is less well studied. We investigated whether medium conditioned by adult hippocampal stem/progenitor cells altered the extent of excitotoxic cell death in hippocampal slice cultures. Conditioned medium significantly reduced cell death following 24 h of exposure to 10 microM NMDA. Neuroprotection was greater in the dentate gyrus, a region neighboring the subgranular zone where stem/progenitor cells reside compared with pyramidal cells of the cornis ammonis. Using mass spectrometric analysis of the conditioned medium, we identified a pentameric peptide fragment that corresponded to residues 26-30 of the insulin B chain which we termed 'pentinin'. The peptide is a putative breakdown product of insulin, a constituent of the culture medium, and may be produced by insulin-degrading enzyme, an enzyme expressed by the stem/progenitor cells. In the presence of 100 pM of synthetic pentinin, the number of mature and immature neurons killed by NMDA-induced toxicity was significantly reduced in the dentate gyrus. These data suggest that progenitors in the subgranular zone may convert exogenous insulin into a peptide capable of protecting neighboring neurons from excitotoxic injury.
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| 6. |
- Geremia-Nievinski, F., et al.
(författare)
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SNR-based GNSS reflectometry for coastal sea-level altimetry: results from the first IAG inter-comparison campaign
- 2020
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Ingår i: Journal of Geodesy. - : Springer Science and Business Media LLC. - 0949-7714 .- 1432-1394. ; 94:8
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Tidskriftsartikel (refereegranskat)abstract
- Ground-based Global Navigation Satellite System Reflectometry (GNSS-R) is quickly maturing toward the objective of becoming a viable alternative for operational coastal sea-level (SL) altimetry in a geocentric reference frame. SL has immense societal implications related to climate change. Of particular interest is the exploitation of existing coastal GNSS sites for reflectometry by means of signal-to-noise ratio (SNR) observables. We report results from the first inter-comparison campaign on SNR-based GNSS-R. The goal was to cross-validate retrieval solutions from independent research groups under comparable conditions. This action was an initiative of the International Association of Geodesy working group 4.3.9 (2015–2019 term). Data collected at the Onsala Space Observatory for a 1-year period (2015–2016) were compared to a co-located tide gauge (TG). SNR data for the GPS L1-C/A signal were processed by four groups, in Sweden, Luxembourg/Brazil, Germany, and the UK. Semidiurnal tidal constituents showed good agreement between TG and all GNSS-R groups. SL variations at diurnal and longer periods were also well captured by all series. Most GNSS-R solutions exhibited spurious tones at integer fractions of one sidereal day, the satellite revisit time of the particular GNSS constellation employed (GPS). Band-pass filtering between 3 h and 30 h confirmed that the dominant tidal components were well captured by most GNSS-R solutions. Higher-frequency SL variations (periods < 3 h) are poorly represented by GNSS-R as a consequence of its low temporal resolution. The solution with the worst agreement neglects a correction associated with the rate of change in sea level and uses narrower satellite elevation ranges per retrieval. Overall, there was excellent agreement, with correlation coefficients exceeding 0.9 and RMSE smaller than 5 cm.
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| 7. |
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| 8. |
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| 9. |
- Hobiger, Thomas, 1978, et al.
(author)
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Ground-based GNSS-R solutions by means of software defined radio
- 2016
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In: Proceedings of the 2016 IEEE International Geoscience and Remote Sensing Symposium (IGARSS 2016). Beijing; China; 10-15 July 2016. - 9781509033324 ; 2016-November, s. Art no 7730472, Pages 5635-5637
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Conference paper (peer-reviewed)abstract
- Usually ground-based GNSS-R installations are either existing geodetic GNSS stations or they are built with dedicated components that enable the deduction and monitoring of physical and geometrical properties of the reflecting area around that particular site. In both cases, hardware components usually enable real-time operation of such instruments. However, as software-defined radio (SDR) technology has advanced in the recent years it is now possible to carry out signal processing in real-time, which makes it an ideal candidate for the realization of a flexible GNSS-R system. It is shown how SDR can help to realize GNSS-R solutions for sea-level monitoring at the Onsala Space Observatory, Sweden. Moreover, such SDR solutions can be mounted on an unmanned aerial vehicle (UAV) in order to collect data from higher altitudes and even provide Delay-Doppler information for extended GNSS-R studies.
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| 10. |
- Hobiger, Thomas, 1978, et al.
(author)
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Inverse modeling of ground-based GNSS-r - Results and new possibilities
- 2017
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In: International Geoscience and Remote Sensing Symposium (IGARSS). ; 2017-July, s. 2671-2681
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Conference paper (peer-reviewed)abstract
- Inverse modeling of ground-based GNSS reflections has the potential to improve existing GNSS-R applications and lead to novel concepts for retrieving geophysical parameters around existing or deliberately built GNSS sites. As we will show in this paper, consistent, accurate and precise determination of sea-surface heights can be realized. Moreover, we demonstrate that it is possible to detect sea-ice freeze states at coastal GNSS sites. In addition, it will be shown how the inverse modeling approach can be used for self-calibration of troposphere delays, which would otherwise bias the target parameters and need to be corrected for by external measurements or data-sets.
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