| 191. |
- Lane, Emma, et al.
(författare)
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Amphetamine-induced abnormal movements occur independently of both transplant- and host-derived serotonin innervation following neural grafting in a rat model of Parkinson's disease.
- 2009
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 35, s. 42-51
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin has been postulated to play a role in the transplant-induced involuntary movements that occur following intrastriatal grafts of ventral mesencephalic tissue in the treatment of Parkinson's disease. Serotonin innervation of the striatum may be derived from either the donor graft tissue or the normal host projections from the midbrain. In two sets of experiments we study the impact of graft- versus host-derived serotonin innervation. All experiments were performed in l-DOPA treated rats with unilateral 6-hydroxydopamine lesions. As expected, following intrastriatal transplantation of embryonic ventral mesencephalon all the transplanted rats exhibited pronounced contralateral rotation in response to amphetamine and some animals also showed severe abnormal involuntary movements (AIMs). In the first set of experiments, all types of AIMs (axial, limb, orolingual and locomotor) were markedly reduced when amphetamine was co-administered with either the D(2) dopamine receptor antagonist raclopride or the D(1) receptor antagonist SCH23390. Cotreatment with the 5-HT(1A) agonist 8-OH-DPAT significantly attenuated the amphetamine-induced axial and limb dyskinesias, whilst locomotor scores remained unchanged. These data point to a major role for dopamine receptors, and to a modulatory role for 5-HT(1A) receptors, in post-grafting dyskinesias. In the second experiment, grafted rats exhibiting amphetamine-induced dyskinesia were subjected to 5,7-dihydroxytryptamine injections into the midbrain in order to destroy the host serotonin innervation. This intervention had no effect on either amphetamine-induced AIMs or contralateral rotation. Histological examination of all grafted rats showed similar numbers of dopaminergic neurons and a very low number of serotonin neurons within the transplants, regardless of AIMs expression. Our results suggest that amphetamine-induced AIMs in grafted animals primarily depend on an activation of dopamine receptors, and that serotonin neurons within either the grafts or the host brain play a negligible role.
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| 192. |
- Lane, Emma, et al.
(författare)
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Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson's disease.
- 2008
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 32, s. 220-228
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Tidskriftsartikel (refereegranskat)abstract
- The observation that neural grafts can induce dyskinesias has severely hindered the development of a transplantation therapy for Parkinson's disease (PD). We addressed the hypothesis that inflammatory responses within and around an intrastriatal graft containing dopamine neurons can trigger dyskinetic behaviors. We subjected rats to unilateral nigrostriatal lesions with 6-hydroxydopamine (6-OHDA) and treated them with L-DOPA for 21 days in order to induce abnormal involuntary movements (AIMs). Subsequently, we grafted the rats with allogeneic embryonic ventral mesencephalic tissue in the dopamine-denervated striatum. In agreement with earlier studies, the grafted rats developed dyskinesia-like AIMs in response to amphetamine. We then used two experimental approaches to induce an inflammatory response and examined if the amphetamine-induced AIMs worsened or if spontaneous AIMs developed. In one experiment, we challenged the neural graft hosts immunologically with an orthotopic skin allograft of the same genetic origin as the intracerebral neural allograft. In another experiment, we infused the pro-inflammatory cytokine interleukin 2 (IL-2) adjacent to the intrastriatal grafts using osmotic minipumps. The skin allograft induced rapid rejection of the mesencephalic allografts, leading to disappearance of the amphetamine-induced AIMs. Contrary to our hypothesis, the rejection process itself did not elicit AIMs. Likewise, the IL-2 infusion did not induce spontaneous AIMs, nor did it alter L-DOPA-induced AIMs. The IL-2 infusions did, however, elicit the predicted marked striatal inflammation, as evidenced by the presence of activated microglia and IL2Ralpha-positive cells. These results indicate that an inflammatory response in and around grafted dopaminergic neurons is not sufficient to evoke dyskinetic behaviors in experimental models of PD.
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| 193. |
- Lane, Emma, et al.
(författare)
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Priming for L-DOPA-induced abnormal involuntary movements increases the severity of amphetamine-induced dyskinesia in grafted rats.
- 2009
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 219, s. 355-358
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Tidskriftsartikel (refereegranskat)abstract
- In some patients, graft-induced dyskinesia develops following intrastriatal transplantation of embryonic neural tissue for the treatment of Parkinson's disease. The mechanisms underlying these involuntary movements need to be clarified before this approach to clinical cell therapy can be developed further. We previously found that rats with 6-OHDA lesions, primed with L-DOPA treatment and that have subsequently undergone intrastriatal graft surgery exhibit involuntary movements when subjected to amphetamine. This model of amphetamine-induced AIMs reflects a pattern of post-graft behaviors that in the absence of robust spontaneous GID in the rat is the closest approximation that we currently have available. We now show that they are associated with the chronic administration of L-DOPA prior to the transplantation surgery. We also demonstrate that neither changes in c-fos nor FosB/DeltaFosB expression in the lateral striatum are associated with the expression of these behaviours. Taken together, these data reveal that the severity of abnormal movements elicited by amphetamine in grafted animals may relate to previous L-DOPA exposure and dyskinesia development, but they develop through mechanisms that are independent of FosB/DeltaFosB upregulation.
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| 194. |
- Lane, Emma, et al.
(författare)
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The impact of graft size on the development of dyskinesia following intrastriatal grafting of embryonic dopamine neurons in the rat.
- 2006
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 22:2, s. 334-345
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Tidskriftsartikel (refereegranskat)abstract
- Intrastriatal transplants of embryonic ventral mesencephalon can cause dyskinesia in patients with Parkinson's disease (PD). We assessed the impact of transplant size on the development of graft-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions were primed to exhibit l-DOPA-induced dyskinesia. They were then intrastriatally grafted with different quantities of embryonic ventral mesencephalic tissue to give small and large grafts. Without drug treatment, discrete dyskinetic-like movements were observed in most rats with large grafts 2–6 weeks after transplantation, but disappeared later. Amphetamine evoked severe abnormal involuntary movements (AIMs) in grafted animals, which were more striking with large grafts. The AIMs coincided with contralateral rotation, but displayed a different temporal profile and pharmacological properties. Thus, selective dopamine uptake blockade elicited rotational behavior, whereas coadministration of both dopamine and serotonin uptake blockers was required to evoke significant orolingual and limb AIMs. In conclusion, robust and reproducible AIMs were evoked in rats with large grafts by blockade of monoamine reuptake. These AIMs may provide a new tool for assessing dyskinetic effects of neural grafting.
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| 195. |
- Lawrence, Akvile, 1976-
(författare)
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Energy Management for Improved Energy Efficiency in the Pulp and Paper Industry : Success Factors for Strengthening Drivers and Overcoming Barriers
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Industrial energy efficiency improves the profit and competitive advantage of companies. The pulp and paper industry (PPI)being one of the five most energy-intensive industries uses 5.6% of global industrial energy, according to the InternationalEnergy Agency. It is one of the key sectors that is faced with the challenge of improving energy efficiency (EE). The PPI isnot less important in Sweden where it uses approximately 52% of the total industrial energy, employing more than 20000people and where improvement of the energy end-use by 1% corresponds to estimated savings of approximately 218 MSEKannually. Energy management (EnM) is a means for improving EE. However, despite research showing the possibility forannual improvement of the energy end-use by 5.5-19.4% by technical measures, EnM is not always used to its full potentialor often hardly implemented, resulting in an EE gap, i.e. the difference between the theoretical practically and cost-effectivelyachievable EE and actual EE. Why then does this EE gap exist? What are the drivers for and barriers to practicing EnM to itsfull potential and thus improving energy efficiency? What are the success factors for encouraging the drivers and overcomingthe barriers? What practical recommendations can be made that could lead to the improvement of energy efficiency? Afterextracting information from historical and current information using tools from multivariate data analysis (MDA), this PhDdissertation presents new knowledge that intends to contribute to overcome the challenges of improving energy efficiency inthe PPI. Specifically, international research primarily addressing EnM in the PPI showed that EnM in the PPI is perceived asEnM via technology, despite that EnM contains other aspects than EnM via technology, e.g. proactive EnM practices. Thisresult indicates the presence of a knowledge-gap on how to deploy EnM in the PPI. Studies on the PPI in Sweden showeddifferent EnM practices among the individual types of mills, i.e. pulp mills, paper mills and integrated-pulp and paper mills.Integrated mills seemed to measure the energy-related performance more than pulp mills and paper mills. However, the resultsalso suggested that the Swedish PPI worked continuously and regularly with EnM. Further, aside from the top ranked perceiveddrivers being economical and the barriers being organizational, knowledge related drivers and barriers were amongst the mostimportant. The results also showed that commonly only selected employees were trained in EnM, which indicated thatcommunication between the trained employees and operations personnel as well as the absorptive capacity for energy issuescould potentially be improved. Additionally, research showed that by using MDA, previously unstudied and unidentifiedconnections could be discovered. Namely, MDA showed that during the ten-year voluntary agreement policy program knownas PFE (Program for improved electricity efficiency in energy-intensive industry), less financially stable and less experiencedwith EnM companies tended to save electricity more than the more financially stable and more EnM experienced companies.Altogether, the success factors for EnM for improving energy efficiency could be summarized in the versatile 4M memorytool - The “4M for energy efficiency”: mind, measure, monitor and manage. The “4M for energy efficiency” suggests that allthe four “Ms” should be practiced simultaneously in order to maximize the achievement of goals of EnM.
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| 196. |
- Lindroth, Anders, et al.
(författare)
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Effects of drought and meteorological forcing on carbon and water fluxes in Nordic forests during the dry summer of 2018
- 2020
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Ingår i: Philosophical Transactions of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic region was subjected to severe drought in 2018 with a particularly long-lasting and large soil water deficit in Denmark, Southern Sweden and Estonia. Here, we analyse the impact of the drought on carbon and water fluxes in 11 forest ecosystems of different composition: spruce, pine, mixed and deciduous. We assess the impact of drought on fluxes by estimating the difference (anomaly) between year 2018 and a reference year without drought. Unexpectedly, the evaporation was only slightly reduced during 2018 compared to the reference year at two sites while it increased or was nearly unchanged at all other sites. This occurred under a 40 to 60% reduction in mean surface conductance and the concurrent increase in evaporative demand due to the warm and dry weather. The anomaly in the net ecosystem productivity (NEP) was 93% explained by a multilinear regression with the anomaly in heterotrophic respiration and the relative precipitation deficit as independent variables. Most of the variation (77%) was explained by the heterotrophic component. Six out of 11 forests reduced their annual NEP with more than 50 g C m(-2)yr(-1)during 2018 as compared to the reference year. The NEP anomaly ranged between -389 and +74 g C m(-2)yr(-1)with a median value of -59 g C m(-2)yr(-1). This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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| 197. |
- Lindstrand, Anna, et al.
(författare)
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From cytogenetics to cytogenomics : whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability
- 2019
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Ingår i: Genome Medicine. - : BMC. - 1756-994X .- 1756-994X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSince different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.MethodsWe analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n=68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n=156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.ResultsFirst, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850kb (min 500bp, max 155Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (>10kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data.Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.ConclusionThe overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
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| 198. |
- Ljungberg, Jessica K., et al.
(författare)
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A Longitudinal Study of Memory Advantages in Bilinguals
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e73029-
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Tidskriftsartikel (refereegranskat)abstract
- Typically, studies of cognitive advantages in bilinguals have been conducted previously by using executive and inhibitory tasks (e.g. Simon task) and applying cross-sectional designs. This study longitudinally investigated bilingual advantages on episodic memory recall, verbal letter and categorical fluency during the trajectory of life. Monolingual and bilingual participants (n= 178) between 35-70 years at baseline were drawn from the Betula Prospective Cohort Study of aging, memory, and health. Results showed that bilinguals outperformed monolinguals at the first testing session and across time both in episodic memory recall and in letter fluency. No interaction with age was found indicating that the rate of change across ages was similar for bilinguals and monolinguals. As predicted and in line with studies applying cross-sectional designs, no advantages associated with bilingualism were found in the categorical fluency task. The results are discussed in the light of successful aging.
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| 199. |
- Ljungberg, Jessika K., et al.
(författare)
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The effect of language skills on dementia in a Swedish longitudinal cohort
- 2016
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Ingår i: Linguistic Approaches to Bilingualism. - : John Benjamins Publishing Company. - 1879-9264 .- 1879-9272. ; 6:1-2, s. 190-204
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings indicate that bilingualism delay the onset of dementia. Using data from the Betula longitudinal cohort study on memory, health and aging (www.betula.su.se) the issue of a possible protective effect of bilingualism was addressed. Monolingual (n = 736) and bilingual (n = 82) participants (= 60 years) without dementia at inclusion were followed for incident dementia over a time-period up to 10 years. In total, 112 participants developed dementia. Analyses were performed with Cox proportional hazards regression adjusted for age, sex, and presence/absence of the Apolipoprotein E (APOE) epsilon 4 allele, with dementia outcome as the dependent variable. Results showed no delayed onset of dementia in bilinguals compared to monolinguals. However, because of the findings from a study using participants from the same population showing beneficial longitudinal effects of bilingualism on episodic memory; we argue that our results may depend on the frequency of use of the second language after retirement.
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| 200. |
- Ludvigsson, Linus, et al.
(författare)
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Carbon Nanotube Emissions from Arc Discharge Production: Classification of Particle Types with Electron Microscopy and Comparison with Direct Reading Techniques.
- 2016
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Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 1475-3162 .- 0003-4878. ; 60:4, s. 493-512
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: An increased production and use of carbon nanotubes (CNTs) is occurring worldwide. In parallel, a growing concern is emerging on the adverse effects the unintentional inhalation of CNTs can have on humans. There is currently a debate regarding which exposure metrics and measurement strategies are the most relevant to investigate workplace exposures to CNTs. This study investigated workplace CNT emissions using a combination of time-integrated filter sampling for scanning electron microscopy (SEM) and direct reading aerosol instruments (DRIs). Material and Methods: Field measurements were performed during small-scale manufacturing of multiwalled carbon nanotubes using the arc discharge technique. Measurements with highly time- and size-resolved DRI techniques were carried out both in the emission and background (far-field) zones. Novel classifications and counting criteria were set up for the SEM method. Three classes of CNT-containing particles were defined: type 1: particles with aspect ratio length:width >3:1 (fibrous particles); type 2: particles without fibre characteristics but with high CNT content; and type 3: particles with visible embedded CNTs. Results: Offline sampling using SEM showed emissions of CNT-containing particles in 5 out of 11 work tasks. The particles were classified into the three classes, of which type 1, fibrous CNT particles contributed 37%. The concentration of all CNT-containing particles and the occurrence of the particle classes varied strongly between work tasks. Based on the emission measurements, it was assessed that more than 85% of the exposure originated from open handling of CNT powder during the Sieving, mechanical work-up, and packaging work task. The DRI measurements provided complementary information, which combined with SEM provided information on: (i) the background adjusted emission concentration from each work task in different particle size ranges, (ii) identification of the key procedures in each work task that lead to emission peaks, (iii) identification of emission events that affect the background, thereby leading to far-field exposure risks for workers other than the operator of the work task, and (iv) the fraction of particles emitted from each source that contains CNTs. Conclusions: There is an urgent need for a standardized/harmonized method for electron microscopy (EM) analysis of CNTs. The SEM method developed in this study can form the basis for such a harmonized protocol for the counting of CNTs. The size-resolved DRI techniques are commonly not specific enough to selective analysis of CNT-containing particles and thus cannot yet replace offline time-integrated filter sampling followed by SEM. A combination of EM and DRI techniques offers the most complete characterization of workplace emissions of CNTs today.
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