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- Aldrin-Kirk, Patrick, et al.
(författare)
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DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor
- 2016
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 90:5, s. 955-968
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clinical trials using transplants of fetal DA neuroblasts have given promising results, although a number of patients have developed graft-induced dyskinesias (GIDs), and the mechanism underlying this troublesome side effect is still unknown. Here we have used a new model where the activity of the transplanted DA neurons can be selectively modulated using a bimodal chemogenetic (DREADD) approach, allowing either enhancement or reduction of the therapeutic effect. We show that exclusive activation of a cAMP-linked (Gs-coupled) DREADD or serotonin 5-HT6 receptor, located on the grafted DA neurons, is sufficient to induce GIDs. These findings establish a mechanistic link between the 5-HT6 receptor, intracellular cAMP, and GIDs in transplanted PD patients. This effect is thought to be mediated through counteraction of the D2 autoreceptor feedback inhibition, resulting in a dysplastic DA release from the transplant.
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- Bergström, Martin, et al.
(författare)
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Sense of coherence: definition and explanation
- 2006
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Ingår i: International Journal of Social Welfare. - : Wiley. - 1369-6866 .- 1468-2397. ; 15:3, s. 219-229
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Tidskriftsartikel (refereegranskat)abstract
- The present study is one of a few that have used "sense of coherence" (SOC) as a dependent variable in an explanatory model. After studying three different samples - 680 students, 180 parents and 315 couples - we conclude that family relational and psychopathological variables contribute significantly to the explanation of SOC (explained variance between 10-27 and 26-50 per cent). In total, we obtained an explained variance of between 42 and 64 per cent. This leads us to the conclusion that in all three samples, SOC is multifaceted and thereby is more than simply an opposite state to depression. Context may play an important part in the explanation of SOC.
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- Birgner, Carolina, et al.
(författare)
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VGLUT2 in dopamine neurons is required for psychostimulant-induced behavioural activation
- 2010
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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. ; 107:1, s. 389-394
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Tidskriftsartikel (refereegranskat)abstract
- The “One neuron-one neurotransmitter” concept has been challenged frequently during the last three decades, and the coexistence of neurotransmitters in individual neurons is now regarded as a common phenomenon. The functional significance of neurotransmitter coexistence is, however, less well understood. Several studies have shown that a subpopulation of dopamine (DA) neurons in the ventral tegmental area (VTA) expresses the vesicular glutamate transporter 2 (VGLUT2) and has been suggested to use glutamate as a cotransmitter. The VTA dopamine neurons project to limbic structures including the nucleus accumbens, and are involved in mediating the motivational and locomotor activating effects of psychostimulants. To determine the functional role of glutamate cotransmission by these neurons, we deleted VGLUT2 in DA neurons by using a conditional gene-targeting approach in mice. A DAT-Cre/Vglut2Lox mouse line (Vglut2f/f;DAT-Cre mice) was produced and analyzed by in vivo amperometry as well as by several behavioral paradigms. Although basal motor function was normal in the Vglut2f/f;DAT-Cre mice, their risk-taking behavior was altered. Interestingly, in both home-cage and novel environments, the gene targeted mice showed a greatly blunted locomotor response to the psychostimulant amphetamine, which acts via the midbrain DA system. Our results show that VGLUT2 expression in DA neurons is required for normal emotional reactivity as well as for psychostimulant-mediated behavioral activation.
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| 7. |
- Bolinder, Martin, et al.
(författare)
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Evaluate carbon stock changes based on the Swedish soil-monitoring program
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the national greenhouse gas inventory, SLU is applying a Tier III method using the Introductory Carbon Balance Model (ICBM) in a holistic framework for calculating changes in soil organic carbon (SOC) stocks in arable land for mineral soils, which Sweden is reporting under the Land Use, Land Use Change and Forestry (LULUCF) sector. This method is delivering SOC stock change rates for eight Swedish agricultural production regions (PO8s), which are aggregated to the national level. The effect of the climate on SOC decomposition in ICBM is accounted for using gridded daily weather records from the Swedish Meteorological Institute (SMHI). The model framework is taking agricultural activity data from yearly census records regarding the use of arable land (area and yield of different crops including fallow) and management systems (straw removal and manure applications). In addition, it applies different empirical functions for estimating annual carbon inputs from roots and for estimating dry soil bulk density for expressing carbon concentrations on a mass basis, based on literature reviews and analyses of large Swedish soil databases. For the ICBM model simulations, initial stocks of SOC are derived from data on soil texture and SOC concentrations from the Swedish Environmental Protection Agency (SEPA) national soil-monitoring program (SMP). The national SMP consists of three soil inventories that periodically characterizes the topsoil properties in 10-year cycles across Sweden. The first inventory, conducted between 1988 and 1995 is providing data for the 1990 baseline, while the latest complete inventory ended 2017. The sampling points in the inventories have coordinates, and data can be associated with each of the Swedish PO8s. We have now been calibrating a new version of the ICBM model by integrating the most recent knowledge gained from long-term field experiments. The objectives of this development project were to evaluate SOC changes from the national SMP by using exact coordinates and new statistical tests and compare these changes to predictions with the new version of ICBM. The general trends in SOC changes calculated from the national SMP remain similar to previous analyses, showing consistent SOC increments over time. The absolute increments at the national level are relatively small, SOC concentrations increased by 0.11, 0.07 and 0.21 percentage units from inventory I to inventory II, from inventory II to inventory III, and from inventory I to inventory III, respectively. This is representing a relative increase of 9.3% between inventory III and I. Applying exact coordinates were allowing us to add a few points in each PO8s that were not present in our previous analysis of the three soil inventories. Using other statistical tests improved the inference between inventories at the PO8 level, where the Wilcoxon signed rank test (a non-parametric method) applied to the matched points when comparing inventory III against II now showed significant differences. The predictions with ICBM are mimicking the relative increase in SOC at the national level but the relative increase is much less pronounced (i.e. 1.5%). Compared to results obtained with the national SMP, ICBM predictions are not always matching the same trends in SOC changes for all of the PO8s. There remain several uncertainties relating to both methods that needs further considerations. For example, data from the Swedish SMP may be associated with inconsistences relating to the use of different analytical methods for measuring SOC concentrations, or to possible under-estimations of SOC concentrations in inventory I due to differences in sampling strategies. While uncertainties relating to ICBM predictions are including e.g. estimation of the amount of annual carbon inputs from roots and manures. A fourth inventory has been initiated and will provide precious information about trends in SOC changes at the national scale, which will be useful for developing both methods.
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- Bolinder, Martin, et al.
(författare)
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Fånggrödor och rötrester i ICBM
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Målsättningen med detta utvecklingsprojekt var att göra en förstudie om tillgänglig statistik för fånggrödor och rötrester. Data med tidsserier för fånggrödor som används i andra modelleringsprojekt på SLU kan anpassas relativt enkelt för att inkluderas i kolbalansmodellen ICBM på länsnivå. För rötrester finns det också potentiella källor med tidsserier, men de skulle kräva lite mer förbehandling innan de kan användas. Båda dataserierna sträcker sig så pass långt bak i tiden att de representerar ganska bra den tidpunkten från och med att dessa två faktorer blir relevanta att ha med i markkolsmodelleringen. Modellparametrar (utöver areal fånggrödor och mängd rötrester), som man skulle behöva justera rör framför allt allometriska funktioner för fånggrödor och humifieringskoefficienten för biogödsel.
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| 9. |
- Bolinder, Martin, et al.
(författare)
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Implementing a new version of ICBM in NIR
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the sector Land Use, Land-Use Change and Forestry (LULUCF, CRF sector 4) within the national greenhouse gas inventory (NIR), Sweden is applying a Tier 3 method for estimating the loss or gain of soil organic carbon (SOC) stocks for cropland on mineral soils to a depth of 0.25 m. The Introductory Carbon Balance Model (ICBM) is used for calculating stock change rates in eight agricultural production regions and results are aggregated to the national level. Calculations involves yearly agricultural census data and daily weather records, as well as results from a national soil-monitoring program (SMP) on soil carbon contents. Initially, only data from the first sampling of the national SMP were used for initializing ICBM. Since the first soil inventory, two additional samplings within the SMP have become available. Simultaneously, we have also gained more knowledge about SOC dynamics. In a development project last year, we were re-analyzing the complete records of data from the last two decades of the SMP confirming that SOC stocks are increasing, and we were starting to calibrate a new version of ICBM. The purpose of the project this year was to implement the new ICBM version in the NIR system.The results show that the new version of ICBM simulates increasing SOC stocks for the period 1990 to 2018, which is thereby more consistent with estimates from the national SMP data than results obtained using the previous ICBM version. The ICBM and SMP assessment methods of SOC stock changes are complementing each other, and both have their inherent limitations. Our analysis with both methodologies are still not fully completed. There remain some fine-tuning in the new ICBM version. Furthermore, we are continuously working on improving the interpretation regarding SOC stocks in the current database from the national SMP. Maintaining the latter and repeating the sampling at least once more would also substantially improve the value of this database.
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| 10. |
- Bolinder, Martin, et al.
(författare)
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New calibration of the ICBM model & analysis of soil organic carbon concentration from Swedish soil monitoring programs
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We are using the Introductory Carbon Balance Model (ICBM) within the national inventory reporting (NIR) system for estimating changes in soil organic carbon (SOC) stocks in Swedish arable land for mineral soils. The first version of ICBM was developing from a long-term experiment (LTE) in Ultuna Sweden, with a time-series of data from 1956 to 1991. The model is initialized using data from a soil database and information from Swedish soil monitoring programs (SMPs). For that purpose, it specifically uses data from the first inventory of the Swedish Environmental Protection Agency (SEPA) SMP conducted in the early 1990s. Since the 1990s, the SEPA SMP has conducted two further inventories in a 10-year cycles, with the last inventory completed in 2017. In complement to this SEPA SMP, the Swedish Board of Agriculture (SJV) was completing a spatially more detailed SMP in 2011 and 2012. In an earlier study, when the third inventory of SEPA was still not fully completed, we showed that SOC concentrations are increasing in Swedish arable mineral soils during the past two decades. Simulations with the current version of ICBM are not reproducing this long-term increasing trend.The main purposes of this project were to (i) calibrate a second version of ICBM by incorporating new knowledge gained from LTEs, (ii) evaluate the trends in SOC concentrations with the complete inventories (I, II and III) of SEPA, (iii) compare results from SEPAs last inventory (III) with that of SJV SMP conducted at approximately the same time period. A Bayesian approach was selected for calibrating the second version of ICBM, using an updated time series of data from Ultuna ending in 2017, and by also including experimental data (1996-2017) from a new sister experiment at Lanna in southern Sweden. For adequately comparing the SEPA and SJV SMPs, we were correcting data from the SJV samples so that we could express all results for SOC concentrations on a basis equivalent to dry combustion. Our analysis on the complete SEPA inventories are generally confirming our previous assessment. However, a more detailed exploration using data only from inventories II and III having identical sampling coordinates, clearly indicates that the increases in SOC concentrations were less in the last decade than in the previous one. Furthermore, when comparing SOC concentrations at different spatial scales, the positive trend in SOC concentrations is much more obvious on the scale of Swedish agricultural production regions (eight regions). Indeed, at the scale of the twenty-one Swedish counties, there are few significant differences and the increasing trend is unclear for many of the counties. This is reflecting difficulties related to the density of sampling points in the SEPA SMP; each of them roughly represents 1500 ha of arable land. Besides, only two decades or even only one decade since SEPA was regarding inventory II as a restart of their SMP, remain a short time period in detecting changes in SOC and highlight the importance of maintaining continuous SMPs.We found the comparisons between the SJV and SEPA SMPs useful but further work is necessary to refine the linkage. The overall changes in parameter values related to SOC dynamics for the calibrated second version of ICBM, will give simulations towards higher SOC stocks, compared to the current version. The main parameter explaining this differences is the increased contribution of below ground (i.e., roots) annual C inputs to soil contributing to the formation of more stable SOC. The approach we used here also offers the advantage of making a multi-site calibration and we could in the future, further refine parameter values by including other Swedish LTEs. Additionally, it allows us to include an estimate for uncertainty in the predictions of SOC stocks, which we could also develop for inclusion in the NIR system.
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