| 1. |
- Björklund, Anders, et al.
(författare)
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Preface
- 2010
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Ingår i: Recent Advances in Parkinson’S Disease Translational and Clinical Research. - 9780444537508 ; 184
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 2. |
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| 3. |
- Dunnett, Stephen B, et al.
(författare)
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Introduction (Part I)
- 2012
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Ingår i: Functional Neural Transplantation III : Primary and stem cell therapies for brain repair. Part 1 - Primary and stem cell therapies for brain repair. Part 1. - 0079-6123. - 9780444595751 ; 200, s. 3-5
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Bokkapitel (refereegranskat)
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| 4. |
- Dunnett, Stephen B, et al.
(författare)
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Introduction (Part II)
- 2012
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Ingår i: Functional Neural Transplantation III : Primary and Stem Cell Therapies for Brain Repair, Part II - Primary and Stem Cell Therapies for Brain Repair, Part II. - 0079-6123. - 9780444595447 ; 201, s. 3-5
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Bokkapitel (refereegranskat)
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| 5. |
- Thompson, Lachlan, et al.
(författare)
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Survival, differentiation, and connectivity of ventral mesencephalic dopamine neurons following transplantation
- 2012
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Ingår i: Functional Neural Transplantation III : Primary and Stem Cell Therapies for Brain Repair, Part I - Primary and Stem Cell Therapies for Brain Repair, Part I. - 0079-6123. - 9780444595751 ; 200, s. 61-95
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Bokkapitel (refereegranskat)abstract
- The reconstruction of midbrain dopamine (DA) circuitry through intracerebral transplantation of new DA neurons contained in embryonic ventral mesencephalon (VM) is a promising therapeutic approach for Parkinson's disease (PD). Although some of the early open-label trials have provided proof-of-principal that VM grafts can provide sustained improvement of motor function in some patients, subsequent trials showed that the functional response can be highly variable. This chapter reviews an extensive body of basic and clinical research on the survival, differentiation, and connectivity of DA neurons in VM grafts, and also looks at how these parameters are affected by certain host- and donor-specific variables. We also review how technical advances in the tools available to study the integration of grafted DA neurons, such as transgenic reporter mice, have made significant contributions to our understanding of the capacity of different DA neuronal subtypes for target-directed growth and innervation of appropriate host brain structures. Our established and on-going understanding of the capacity of grafted DA neurons to structurally and functionally integrate following transplantation forms an important basis for the refinement and optimization of VM grafting procedures, and also the development of new procedures based on the use of stem cells.
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| 6. |
- Björklund, Anders, 1950-, et al.
(författare)
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Arbetsmarknaden
- 2014. - 4
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Bok (övrigt vetenskapligt/konstnärligt)
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| 7. |
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| 8. |
- Björklund, Anders, et al.
(författare)
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Gene therapy for dopamine replacement in Parkinson's disease.
- 2009
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 1:2, s. 2-2
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of L-dopa (L-3,4-dihydroxyphenylalanine) therapy 40 years ago was a revolution in the treatment of patients with Parkinson s disease (PD). With time, however, the shortcomings of oral L-dopa medication became apparent, in particular the appearance of troublesome side effects, expressed as involuntary movements (dyskinesias) that developed over time in many patients. A gene therapy approach, aimed at restoring dopamine synthesis in the affected brain by viral vector delivery of genes that encode the dopamine-synthesizing enzymes, may offer a solution to this problem. Now, a team of French and UK researchers reports promising results in a nonhuman primate model of PD, paving the way for clinical trials of this enzyme-replacement approach.
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| 9. |
- Björklund, Anders, et al.
(författare)
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Gene therapy for Parkinson's disease shows promise.
- 2011
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 3:79, s. 1-79
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Tidskriftsartikel (refereegranskat)abstract
- A gene therapy trial for Parkinson's disease met its primary endpoint, but challenges remain.
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| 10. |
- Böhlmark, Anders, 1973-
(författare)
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School Reform, Educational Achievement and Lifetime Income : Essays in Empirical Labor Economics
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Impact of School Choice on Pupil Achievement, Segregation and Costs: Swedish Evidence. This paper evaluates school choice at the compulsory school level. We estimate the impact of an increased enrolment in private schools on average achievement using within-municipality variation over time. We find positive effects, shown to be the sum of a (small) private school attendance effect and a competition effect. We also find effects on segregation and costs.Age at Immigration and School Performance: A Siblings Analysis Using Swedish Register Data. This paper analyzes the role of age at immigration for the school performance gap between native and immigrant pupils by exploiting within-family variation. The critical age is about nine, above which there is a strong negative impact on performance. The results are similar for boys and girls, but vary by region of origin. A comparison of sibling-difference and cross-sectional estimates reveals striking similarities. Integration of Childhood Immigrants in the Short and in the Long Run: Swedish Evidence. I study childhood immigrants at different stages in life in order to examine the role of age at immigration for educational and labor market outcomes. I find that childhood immigrants tend later to recover strongly in terms of educational achievement. Yet, the same individuals are on average found to be poorly integrated into the labor market. Life-Cycle Variations in the Association between Current and Lifetime Income: Replication and Extension for Sweden. We apply a generalized errors-in-variables model, recently developed by Steven Haider and Gary Solon, in order to produce estimates of the association between current and lifetime income. We find strong life-cycle patterns. This implies that the widespread use of current income as a proxy for lifetime income leads to inconsistent estimates even when the proxy is used as the dependent variable. We find country similarities, but gender and cohort differences.
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| 11. |
- Holmlund, Bertil, et al.
(författare)
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Arbetsmarknaden
- 2006
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Bok (populärvet., debatt m.m.)
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| 12. |
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| 13. |
- Hägglund, Pathric, 1971-
(författare)
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Natural and Classical Experiments in Swedish Labour Market Policy
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- "Effects of Changes in the Unemployment Insurance Eligibility Requirements on Job Duration — Swedish Evidence" This paper investigates the impact of the unemployment insurance (UI) entrance requirement on employment duration among earlier unemployed in Sweden. I exploit changes in the rule taking place in 1994 and 1997 to study behavioural adjustments in the timing of job separation between 1992, 1996, and 1998. Performing across-year analyses, I find evidence of clustering of job exits at the time of UI qualification. By using predicted hazard rates for each week, I calculate an approximate 2.9-week extension in average employment duration between 1996 and 1998 due to the 5-week prolonging of the entrance requirement. "Job-search Assistance Using the Internet – Experiences from a Swedish Randomised Experiment" This paper reports the experience from a randomised experiment offering voluntary job-search assistance on the Internet to job seekers at Swedish public employment offices. The purpose is to, i) investigate to what extent the evaluation design manages to avoid common difficulties in experimental evaluation, ii) assess the effect of the programme on the employment outcome, and iii) use the nonbiased experimental results as a benchmark evaluating the performance of frequent nonexperimental estimators. I find that the evaluation design successfully circumvents inherent difficulties in the experimental approach, such as ethical concerns, bureaucratic behaviour and randomisation bias. However, the voluntariness of the programme caused severe compliance problems in terms of both no-shows and dropouts. This is accounted for by analysing the effect of the “intent-to-treat” (the policy parameter of most interest), which is close to zero. Studying the effects of various doses of actual treatment, using an nonexperimental instrumental variable model, I fail to reject the hypothesis of a zero programme effect. Finally, a methodological comparison suggests that standard nonexperimental techniques succeed in reproducing the nonbiased experimental results. "Are there Pre-programme Effects of Swedish Active Labour Market Policies – Evidence from Three Randomised Experiments" This paper takes advantage of unique experimental data from three demonstration programmes in 2004 to investigate pre-programme incentive effects of active placement efforts at the employment offices in Sweden. The exit rate from unemployment between referral to and start of the programme services is compared between UI eligible experiment and control group members. The results are mixed. In one of the experiments, targeted towards a broad group of UI receivers, arranged job-search activities in groups combined with increased monitoring of job-search efforts generated a 38 per cent increase in the escape rate from unemployment in the weeks leading up to programme start. This translates into an almost two-week reduction of the ongoing UI spell. Referrals to increased monitoring alone did not have the same effect on exit behaviour. In the other two experiments, targeted towards youth and highly educated respectively, referrals to active placement efforts had no effect on the pre-programme outflow.
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| 14. |
- Lönnermark, Anders, 1968-, et al.
(författare)
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CFD-simulation of under-ventilated fires - Comparison to experimental results
- 2009
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- To investigate how different configurations in a large room affect the smoke spread andtemperature during a fire, eleven tests were performed. The tests scenario was built in scale1:2 and can be described as a large room with small ventilation openings near the floor. Thefire tests were simulated using the CFD (computational fluid dynamics) code FDS (FireDynamics Simulator). To see how well FDS simulates under-ventilated fires, both wellventilated and under-ventilated cases were selected for the validation. Gas temperaturesand oxygen concentrations for the experiments and the simulations, respectively, arecompared. The results of the validation show that the combustion model (mixture fractioncombustion model), with empirical amendments for when the fire is allowed to burn, is verysensitive to changes in the oxygen level.
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| 15. |
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| 16. |
- Lönnermark, Anders, 1968-, et al.
(författare)
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Smoke Spread and Gas Temperatures during Fires in Retail Premises - Experiments and CFD Simulations
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In analytical solutions, e.g. for evacuation design, the use of computer programs for simulating the smoke spread is common. In recent years a group of computer codes named CFD (Computational Fluid Dynamics) codes has emerged as an engineering tool for describing smoke spread. The CFD codes need to be compared against experimental data so that they can be fully validated. To investigate how different configurations in a retail premises affect the smoke spread and temperatures during a fire, 11 tests were performed. The tests scenario was built in scale 1:2 and can be described as a large room with small ventilation openings near the floor. The configuration parameters were: different fire sizes, different fire positions and different shelf configurations. Heptane pools were used to represent the fires. Three different fire sizes were used and during the test with the largest fire size, 650 mm × 650 mm, the test conditions became under-ventilated, i.e., there was insufficient oxygen available to allow stoichiometric combustion of all evaporated fuel. For the simulations conducted as part of this work, the focus was on under-ventilated fires. However, the experimental results for all of the tests are presented and discussed. The fire tests were simulated using the CFD code FDS (Fire Dynamics Simulator). To see how well FDS simulates under-ventilated fires, both well ventilated and under-ventilated cases were selected for the validation. Gas temperatures and oxygen concentration for the experiments and the simulations, respectively, are compared. Different types of meshes for the simulations and different ways of modelling the fire were used. The results of the validation show that the combustion model (mixture fraction combustion model) with empirical amendments for when the fire is allowed to burn, is very sensitive to changes in the oxygen level. The comparison between the experimental data and the simulation indicates that FDS easily can underestimate the oxygen level and thereby the heat release rate which, in turn, creates an underestimation of the temperatures. The validation has shown that the simple empirical expression used for when the fire is allowed to burn is very sensitive and if used without proper understanding it may produce large differences between the experiments and the simulations. It is also clear that the temperatures for well ventilated cases may be overestimated and that the use of visibility and toxicity (soot and carbon monoxide yields) are related to uncertainties. It should also be noted that there are cases where the temperature from the simulations and the temperature measurements correspond relatively well with each other and yet other cases when the simulated temperature is higher than the measured temperature. This depends on the simulation case, the position in the set-up and the time period compared.
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| 17. |
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| 18. |
- Malinowsky, Camilla, et al.
(författare)
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Differences in the use of everyday technology among persons with MCI, SCI and older adults without known cognitive impairment
- 2017
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Ingår i: International psychogeriatrics. - : Cambridge University Press. - 1041-6102 .- 1741-203X. ; 29:7, s. 1193-1200
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Tidskriftsartikel (refereegranskat)abstract
- Background: To use valid subjective reports sensible to cognitive decline is vital to identify very early signs of dementia development. Use of everyday technology (ET) has been shown to be sensitive to differentiate adults with mild cognitive impairment (MCI) from controls, but the group with subjective cognitive impairment (SCI) has not yet been examined. This study aims to investigate and compare self-perceived ability in ET use and number of ETs reported as actually used in a sample of older adults with SCI, MCI, and older adults with no known cognitive impairment, i.e. controls.Methods: Older adults with MCI (n = 29), SCI ( n = 26), and controls (n = 30) were interviewed with the short version of the Everyday Technology Use Questionnaire (S-ETUQ) to capture self-perceived ability in ET use and number of ETs used. To generate individual measures of ability to use ET, Rasch analysis was used. The measures were then compared group-wise using ANCOVA. The numbers of ETs used were compared group-wise with ANOVA.Results: Controls versus SCI and MCI differed significantly regarding ETs reported as used, but not SCI versus MCI. Similarly, in ability to use ET, controls versus SCI and MCI differed significantly but not SCI versus MCI.Conclusions: The significantly lower numbers of ETs reported as actually used and the lower ability in SCI and MCI groups compared to controls suggest that ET use is affected already in very minor cognitive decline. This indicates that self-reported ET use based on the S-ETUQ is sensitive to detect changes already in SCI.
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| 19. |
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| 20. |
- Parmar, Malin, et al.
(författare)
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In vivo conversion of dopamine neurons in mouse models of Parkinson's disease - a future approach for regenerative therapy?
- 2021
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Ingår i: Current Opinion in Genetics & Development. - : Elsevier BV. - 1879-0380 .- 0959-437X. ; 70, s. 76-82
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Forskningsöversikt (refereegranskat)abstract
- Recent advances in cell reprogramming have made it possible to form new therapeutic cells within the body itself via a process called direct conversion or lineage reprogramming. A series of studies have shown that it is possible to reprogram resident glia into new neurons within the brain parenchyma. These studies opened up for the targeted attempts to achieve functional brain repair using in vivo conversion. Because of the relatively focal degeneration, Parkinson's Disease (PD) is an attractive target for both transplantation-based and in vivo conversion-based reparative approaches. Fetal cell transplants have provided proof-of-concept and stem cell-based therapies for PD are now on the verge of entering clinical trials. In the future, in vivo conversion may be an alternative to transplantation-based therapies.
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| 21. |
- Rosenblad, Carl, et al.
(författare)
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Vector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson's disease
- 2019
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; , s. 2402-2416
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Tidskriftsartikel (refereegranskat)abstract
- Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the leading standard medication for patients with Parkinson's disease. With time, however, the shortcomings of oral l-DOPA treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. These side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-DOPA in a more continuous manner. Local gene delivery of the l-DOPA synthesizing enzymes, tyrosine hydroxylase and guanosine-tri-phosphate-cyclohydrolase-1, offers a new approach to a more refined dopaminergic therapy where l-DOPA is delivered continuously at the site where it is needed i.e. the striatum. In this study we have explored the therapeutic efficacy of adeno-associated viral vector-mediated l-DOPA delivery to the putamen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys, the standard non-human primate model of Parkinson's disease. Viral vector delivery of the two enzymes, tyrosine hydroxylase and guanosine-5'-tri-phosphate-cyclohydrolase-1, bilaterally into the dopamine-depleted putamen, induced a significant, dose-dependent improvement of motor behaviour up to a level identical to that obtained with the optimal dose of peripheral l-DOPA. Importantly, this improvement in motor function was obtained without any adverse dyskinetic effects. These results provide proof-of-principle for continuous vector-mediated l-DOPA synthesis as a novel therapeutic strategy for Parkinson's disease. The constant, local supply of l-DOPA obtained with this approach holds promise as an efficient one-time treatment that can provide long-lasting clinical improvement and at the same time prevent the appearance of motor fluctuations and dyskinetic side effects associated with standard oral dopaminergic medication.
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| 22. |
- Aaberge, Rolf, et al.
(författare)
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Income Inequality and Income Mobility in the Scandinavian Countries Compared to the United States
- 2002
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Ingår i: The Review of Income and Wealth. - : Blackwell Publishers Ltd. - 1475-4991 .- 0034-6586. ; 48:4, s. 443-469
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Tidskriftsartikel (refereegranskat)abstract
- This paper compares income inequality and income mobility in the Scandinavian countries and the United States during 1980-90. The results suggest that inequality is greater in the United States than in the Scandinavian countries and that this inequality ranking of countries remains unchanged when the accounting period of income is extended from one to eleven years. The pattern of mobility turns out to be remarkably similar, in the sense that the proportionate reduction in inequality from extending the accounting period of income is much the same. But we do find evidence of greater dispersion of first differences of relative earnings and income in the United States. Relative income changes are associated with changes in labor market and marital status in all four countries, but the magnitude of such changes are largest in the United States.
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| 23. |
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| 24. |
- Adler, Andrew F., et al.
(författare)
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hESC-Derived Dopaminergic Transplants Integrate into Basal Ganglia Circuitry in a Preclinical Model of Parkinson's Disease
- 2019
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:13, s. 5-3473
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Tidskriftsartikel (refereegranskat)abstract
- Cell replacement is currently being explored as a therapeutic approach for neurodegenerative disease. Using stem cells as a source, transplantable progenitors can now be generated under conditions compliant with clinical application in patients. In this study, we elucidate factors controlling target-appropriate innervation and circuitry integration of human embryonic stem cell (hESC)-derived grafts after transplantation to the adult brain. We show that cell-intrinsic factors determine graft-derived axonal innervation, whereas synaptic inputs from host neurons primarily reflect the graft location. Furthermore, we provide evidence that hESC-derived dopaminergic grafts transplanted in a long-term preclinical rat model of Parkinson's disease (PD) receive synaptic input from subtypes of host cortical, striatal, and pallidal neurons that are known to regulate the function of endogenous nigral dopamine neurons. This refined understanding of how graft neurons integrate with host circuitry will be important for the design of clinical stem-cell-based replacement therapies for PD, as well as for other neurodegenerative diseases. Adler et al. graft hESC-derived dopaminergic progenitors into a rat model of Parkinson's disease. They find grafts correctly innervate host targets and receive appropriate synaptic input after intranigral and intrastriatal placement. Furthermore, the same host neurons projecting toward endogenous dopamine neurons are found to also connect to the grafts.
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| 25. |
- Adler, Andrew, et al.
(författare)
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Transsynaptic tracing and its emerging use to assess graftreconstructed neural circuits
- 2020
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 38:6, s. 716-726
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Tidskriftsartikel (refereegranskat)abstract
- Fetal neural progenitor grafts have been evaluated in preclinical animal models of spinal cord injury and Parkinson’s disease for decades, but the initial reliance on primary tissue as a cell source limited the scale of their clinical translatability. With the development of robust methods to differentiate human pluripotent stem cells to specific neural subtypes, cell replacement therapy holds renewed promise to treat a variety of neurodegenerative diseases and injuries at scale. As these cell sources are evaluated in preclinical models, new transsynaptic tracing methods are making it possible to study the connectivity between host and graft neurons with greater speed and detail than was previously possible. To date, these studies have revealed that widespread, long-lasting, and anatomically-appropriate synaptic contacts are established between host and graft neurons, as well as new aspects of host-graft connectivity which may be relevant to clinical cell replacement therapy. It is not yet clear, however, whether the synaptic connectivity between graft and host neurons is as celltype specific as it is in the endogenous nervous system, or whether that connectivity is responsible for the functional efficacy of cell replacement therapy. Here, we review evidence suggesting that the new contacts established between host and graft neuronsmay indeed be cell-type specific, and how transsynaptic tracing can be used inthe future to further elucidate the mechanisms of graft-mediated functional recovery in spinal cord injury and Parkinson’s disease.
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| 26. |
- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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Design and Synthesis of BACE-1 Inhibitors Containing a New Hydroxyethylene (HE) Scaffold: Potent activities in a cellular assay
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In a preceding report from our group we disclosed the development of a novel HE transition state isostere with a difluorophenoxymethyl side chain in the P1 position and a methoxy group in the P1’ position furnishing highly potent inhibitors of BACE-1 (i.e. lead compound 1), which moreover exhibit very promising selectivity over cathepsin D. In a continuation of this work with the aim at improving on the cell-based activity and pharmacokinetic properties, we have further developed the SAR for the P1 side chain of inhibitor 1 whereby the P1 side chain oxygen has been substituted for an amine, a carbon or a bond. The chemistry developed for the previous HE inhibitor structure 1 has now been extended to readily accommodate the introduction of new P1 side chains into this new HE scaffold. These modifications have given rise to several highly potent inhibitors where the most potent displayed a BACE-1 Ki value of 0.2 nM and a cell-based Aβ40 IC50 value of 9 nM. Thus, regarding the enzyme inhibition in the cell assay a more than 600-fold improvement compared to compound 1 was achieved via minor structural alterations.
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| 27. |
- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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P2 '-truncated BACE-1 inhibitors with a novel hydroxethylene-like core
- 2010
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 45:2, s. 542-554
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Tidskriftsartikel (refereegranskat)abstract
- Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields.
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| 28. |
- Aguilar, Ximena, 1978-, et al.
(författare)
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Interaction Studies of the Human and Arabidopsis thaliana Med25-ACID Proteins with the Herpes Simplex Virus VP16-and Plant-Specific Dreb2a Transcription Factors
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:5, s. e98575-
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Tidskriftsartikel (refereegranskat)abstract
- Mediator is an evolutionary conserved multi-protein complex present in all eukaryotes. It functions as a transcriptional coregulator by conveying signals from activators and repressors to the RNA polymerase II transcription machinery. The Arabidopsis thaliana Med25 (aMed25) ACtivation Interaction Domain (ACID) interacts with the Dreb2a activator which is involved in plant stress response pathways, while Human Med25-ACID (hMed25) interacts with the herpes simplex virus VP16 activator. Despite low sequence similarity, hMed25-ACID also interacts with the plant-specific Dreb2a transcriptional activator protein. We have used GST pull-down-, surface plasmon resonance-, isothermal titration calorimetry and NMR chemical shift experiments to characterize interactions between Dreb2a and VP16, with the hMed25 and aMed25-ACIDs. We found that VP16 interacts with aMed25-ACID with similar affinity as with hMed25-ACID and that the binding surface on aMed25-ACID overlaps with the binding site for Dreb2a. We also show that the Dreb2a interaction region in hMed25-ACID overlaps with the earlier reported VP16 binding site. In addition, we show that hMed25-ACID/Dreb2a and aMed25-ACID/Dreb2a display similar binding affinities but different binding energetics. Our results therefore indicate that interaction between transcriptional regulators and their target proteins in Mediator are less dependent on the primary sequences in the interaction domains but that these domains fold into similar structures upon interaction.
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| 29. |
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| 30. |
- Ahrné, Karin, et al.
(författare)
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Rödlista över fjärilar Lepidoptera
- 2015
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Ingår i: Rödlistade arter i Sverige 2015. - Uppsala : ArtDatabanken SLU. - 9789187853104 ; , s. 98-112
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 31. |
- Albrecht, James, et al.
(författare)
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Unionization and the Evolution of the Wage Distribution in Sweden : 1968 to 2000
- 2011
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Ingår i: Industrial & labor relations review. - 0019-7939 .- 2162-271X. ; 64:5, s. 1039-1057
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Tidskriftsartikel (refereegranskat)abstract
- Using the 1968, 1981, and 2000 Swedish Level of Living Surveys, the authors examine the evolution of the wage distribution in Sweden over the periods 1968–1981 and 1981–2000. The first period was the heyday of the Swedish solidarity wage policy with strong equalization clauses in the central wage agreements. During the second period, there was more flexibility for firms to adjust wages to reflect conditions such as labor shortages in particular fields. The authors find a remarkable narrowing of the wage distribution in the first period, but in the second period, wages grew more equally across the distribution. The authors decompose these changes in wages across the distribution into two components—those due to changes in the distribution of characteristics such as education and experience and those due to changes in the distribution of returns to those characteristics. They find that the wage compression between 1968 and 1981 was driven by changes in the distribution of returns, but between 1981 and 2000, the change in the distribution of returns had less of an effect on wage compression.
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| 32. |
- Aldén, Lina, 1979-, et al.
(författare)
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Early health and school outcomes for children with lesbian parents : evidence from Sweden
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sweden was early to legalize same-sex partnership (1995), to allow same-sex couples to adopt children (2003), and to offer same-sex couples fertility treatment through the national health system (2005). Using population data, we identify children of lesbian parents as those whose biological mother was a registered same-sex partner no later than six months after the child's birth. The number of such children increased markedly from 1995 to 2010 with a total of 750 children for the whole period. We find that boys and girls with lesbian parents had 2.4 percent lower birth weight than other children, a difference that is statistically significant from zero at the 5 percent level. Girls, but not boys, also have a higher probability of having a low birth weight. We follow these children until age ten and observe diseases of the respiratory system. Boys with lesbian parents have a significantly lower probability of such diseases (-3.4 percentage points), and girls with lesbian parents an insignificantly higher probability (+2.4 percentage points). Our analysis of school outcomes at age ten uses a small sample so precision is low. The point estimates show that boys with lesbian parents outperform other children by around 10 percentiles higher test scores in Math and Swedish. These differences are barely significant, while estimates for girls are lower and not significant. For all outcomes, we find that children with lesbian parents benefit from their mother's socio-economic status, whereas they suffer in terms of birth weight from having been exposed to fertility treatment.
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| 33. |
- Alvarsson, A, et al.
(författare)
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Emotional memory impairments induced by AAV-mediated overexpression of human α-synuclein in dopaminergic neurons of the ventral tegmental area.
- 2016
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 296, s. 129-133
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is associated with extensive degeneration of dopaminergic neurons originating in the substantia nigra pars compacta, but neuronal loss is also found in the ventral tegmental area (VTA). The VTA projects to areas involved in cognitive and emotional processes, including hippocampus, amygdala, nucleus accumbens and prefrontal cortex, and has thus been proposed to play a role in emotional memory impairments in PD. Since the formation of α-synuclein inclusions throughout the central nervous system is a pathological hallmark of PD, we studied the progressive effects of α-synuclein overexpression in the VTA on motor functions, emotional behaviour and emotional memory. Adeno-associated viral (AAV) vectors encoding either human α-synuclein or green fluorescent protein (GFP) were injected stereotactically into the VTA, and behaviour was monitored 3 and 8 weeks following AAV injection. At week 8, there was a 22% reduction of TH+ neurons in the VTA. We demonstrate that α-synuclein overexpression in dopaminergic neurons of the VTA induced mild motor deficits that appeared 3 weeks following AAV-α-synuclein injection and were aggravated at week 8. No depressive- or anxiety-like behaviours were found. To address emotional memory, we used the passive avoidance test, a one-trial associative learning paradigm based on contextual conditioning which requires minimal training. Interestingly, emotional memory impairments were found in α-synuclein overexpressing animals at week 8. These findings indicate that α-synuclein overexpression induces progressive memory impairments likely caused by a loss of function of mesolimbic dopaminergic projections.
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| 34. |
- Andersson, Elin, et al.
(författare)
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Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2.
- 2006
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Ingår i: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 1477-9129. ; 133:3, s. 507-516
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Tidskriftsartikel (refereegranskat)abstract
- Neurogenin 2 (Ngn2) is a proneural gene involved in neuronal differentiation and subtype specification in various regions of the nervous system. In the ventral midbrain, Ngn2 is expressed in a spatiotemporal pattern that correlates with the generation of mesencephalic dopaminergic (mesDA) neurons. We show here that lack of Ngn2 impairs the development of mesDA neurons, such that less than half of the normal mesDA neuron number remain in Ngn2 mutant mice at postnatal stages. Analysis of Ngn2 mutant mice during mesDA neurogenesis show that medially located precursors are formed but are arrested in their differentiation at a stage when they have not yet acquired the characteristics of mesDA neuron precursors. Loss of Ngn2 function appears to specifically affect the generation of DA neurons, as the development of other types of neurons within the ventral midbrain is unaltered. Ngn2 is the first example of a gene expressed in progenitors in the ventricular zone of the mesDA neuron domain that is essential for proper mesDA neuron differentiation, and whose loss of function causes impaired mesDA neurogenesis without other major abnormalities in the ventral midbrain.
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| 35. |
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| 36. |
- Andersson, Sören, et al.
(författare)
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Frictions models for sliding dry, boundary and mixed lubricated contacts
- 2007
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Ingår i: Tribology International. - : Elsevier BV. - 0301-679X .- 1879-2464. ; 40, s. 580-587
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Tidskriftsartikel (refereegranskat)abstract
- Friction, lubrication, and wear have a strong influence on the performance and behavior of mechanical systems. This paper deals with different friction models for sliding contacts running under different conditions. The models presented are suited to different situations, depending on the type of contact, running conditions, and the behavior of interest. The models will be discussed from simulation and tribological points of view. The different types of friction models considered are:center dot friction models for transient sliding under dry, boundary and mixed lubrication conditions,center dot friction models for micro-displacements of engineering surfaces subjected to transient sliding,center dot friction models often used in the simulation and control of technical systems,center dot combined friction models that represent physical behaviors fairly well but are also suitable for use in simulating systems,center dot friction models that take into account the stochastic nature of interacting surface asperities
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| 37. |
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| 38. |
- Angot, Elodie, et al.
(författare)
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Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Several people with Parkinson's disease have been treated with intrastriatal grafts of fetal dopaminergic neurons. Following autopsy, 10-22 years after surgery, some of the grafted neurons contained Lewy bodies similar to those observed in the host brain. Numerous studies have attempted to explain these findings in cell and animal models. In cell culture, α-synuclein has been found to transfer from one cell to another, via mechanisms that include exosomal transport and endocytosis, and in certain cases seed aggregation in the recipient cell. In animal models, transfer of α-synuclein from host brain cells to grafted neurons has been shown, but the reported frequency of the event has been relatively low and little is known about the underlying mechanisms as well as the fate of the transferred α-synuclein. We now demonstrate frequent transfer of α-synuclein from a rat brain engineered to overexpress human α-synuclein to grafted dopaminergic neurons. Further, we show that this model can be used to explore mechanisms underlying cell-to-cell transfer of α-synuclein. Thus, we present evidence both for the involvement of endocytosis in α-synuclein uptake in vivo, and for seeding of aggregation of endogenous α-synuclein in the recipient neuron by the transferred α-synuclein. Finally, we show that, at least in a subset of the studied cells, the transmitted α-synuclein is sensitive to proteinase K. Our new model system could be used to test compounds that inhibit cell-to-cell transfer of α-synuclein and therefore might retard progression of Parkinson neuropathology.
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| 39. |
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| 40. |
- Baranowska, Julia, et al.
(författare)
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Associations between medical therapy after surgical aortic valve replacement for aortic stenosis and long-term mortality: a report from the SWEDEHEART registry.
- 2022
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Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 8:8, s. 837-846
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Tidskriftsartikel (refereegranskat)abstract
- The association between use of statins, renin-angiotensin system (RAS) inhibitors and/or β-blockers and long-term mortality in patients with aortic stenosis who underwent surgical aortic valve replacement (SAVR) is unknown.All patients with aortic stenosis who underwent isolated first time SAVR in Sweden from 2006 to 2017 and survived six months after discharge were included. Individual patient data from four mandatory nationwide registries were merged. Cox proportional hazards models, with time-updated data on medication status and adjusted for age, sex, comorbidities, type of prosthesis, and year of surgery, were used to investigate associations between dispensed statins, RAS inhibitors, and β-blockers, and all-cause mortality. In total, 9553 patients were included, and median follow-up time was 4.9 years (range 0-11); 1738 patients (18.2%) died during follow-up. Statins were dispensed to 49.1% and 49.0% of the patients within six months of discharge from hospital and after ten years, respectively. Corresponding figures were 51.4% and 53.9% for RAS inhibitors, and 79.3% and 60.7% for β-blockers. Ongoing treatment was associated with lower mortality risk for statins [adjusted hazard ratio (aHR) 0.67 (95% confidence interval 0.60-0.74), p<0.001] and RAS inhibitors [aHR 0.84 (0.76-0.93), p<0.001] but not for β-blockers [aHR 1.17 (1.05-1.30), p=0.004]. The associations were robust in subgroups based on age, sex, and comorbidities (p for interactions>0.05).The results of this large population-based real-world study support the use of statins and RAS inhibitors for patients who underwent SAVR due to aortic stenosis.
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| 41. |
- Barker, Roger A, et al.
(författare)
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Animal Models of Parkinson's Disease : Are They Useful or Not?
- 2020
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 10:4, s. 1335-1342
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Forskningsöversikt (refereegranskat)abstract
- The use of animal models in Parkinson's disease research has been controversial in terms of how well they relate to the clinical condition and thus their utility for translating therapies from the lab to the clinic. In this article, two researchers debate this issue with Roger Barker taking the view that such models are not useful and may even be misleading, while Anders Björklund defends their use and highlights their value in better understanding and treating this condition.
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| 42. |
- Barker, Roger A, et al.
(författare)
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Are Stem Cell-Based Therapies for Parkinson's Disease Ready for the Clinic in 2016?
- 2016
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 6:1, s. 57-63
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Tidskriftsartikel (refereegranskat)abstract
- Recent news of an impending clinical cell transplantation trial in Parkinson's disease using parthenogenetic stem cells as a source of donor tissue have raised hopes in the patient community and sparked discussion in the research community. Based on discussions held by a global collaborative initiative on translation of stem cell therapy in Parkinson's disease, we have identified a set of key questions that we believe should be addressed ahead of every clinical stem cell-based transplantation trial in this disorder. In this article, we first provide a short history of cell therapy in Parkinson's disease and briefly describe the current state-of-art regarding human stem cell-derived dopamine neurons for use in any patient trial. With this background information as a foundation, we then discuss each of the key questions in relation to the upcoming therapeutic trial and critically assess if the time is ripe for clinical translation of parthenogenetic stem cell technology in Parkinson's disease.
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| 43. |
- Barker, Roger A., et al.
(författare)
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Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials.
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| 44. |
- Barker, Roger A., et al.
(författare)
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GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop
- 2020
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 10:3, s. 875-891
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Tidskriftsartikel (refereegranskat)abstract
- The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.
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| 45. |
- Barker, Roger A., et al.
(författare)
-
Restorative cell and gene therapies for Parkinson's disease
- 2023
-
Ingår i: Precision Medicine in Neurodegenerative Disorders, Part II. - 0072-9752 .- 2212-4152. - 9780323855556 ; 193, s. 211-226
-
Bokkapitel (refereegranskat)abstract
- One of the core pathological features of Parkinson's disease (PD) is the loss of the dopaminergic nigrostriatal pathway which lies at the heart of many of the motor features of this condition as well as some of the cognitive problems. The importance of this pathological event is evident through the clinical benefits that are seen when patients with PD are treated with dopaminergic agents, at least in early-stage disease. However, these agents create problems of their own through stimulation of more intact dopaminergic networks within the central nervous system causing major neuropsychiatric problems including dopamine dysregulation. In addition, over time the nonphysiological stimulation of striatal dopamine receptors by L-dopa containing drugs leads to the genesis of L-dopa-induced dyskinesias that can become very disabling in many cases. As such, there has been much interest in trying to better reconstitute the dopaminergic nigrostriatal pathway using either factors to regrow it, cells to replace it, or gene therapies to restore dopamine transmission in the striatum. In this chapter, we lay out the rationale, history and current status of these different therapies as well as highlighting where the field is heading and what new interventions might come to clinic in the coming years.
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| 46. |
- Barker, Roger A, et al.
(författare)
-
Stem Derived Dopamine Neurons : Will They Replace DBS as the Leading Neurosurgical Treatment for Parkinson's Disease?
- 2021
-
Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 11:3, s. 909-917
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Tidskriftsartikel (refereegranskat)abstract
- The use of stem cell derived dopamine neurons for treating patients with Parkinson's disease has now evolved to the first in human clinical trials. In this debate, we argue that assuming these trials give positive outcomes that this therapy will supercede DBS as the neurosurgical treatment of choice for PD patients in the future given it is a one-off therapy that repairs a critical pathway in the parkinsonian brain.
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| 47. |
- Barker, Roger A, et al.
(författare)
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The history and status of dopamine cell therapies for Parkinson's disease
-
Ingår i: BioEssays. - 0265-9247.
-
Forskningsöversikt (refereegranskat)abstract
- Parkinson's disease (PD) is characterized by the loss of the dopaminergic nigrostriatal pathway which has led to the successful development of drug therapies that replace or stimulate this network pharmacologically. Although these drugs work well in the early stages of the disease, over time they produce side effects along with less consistent clinical benefits to the person with Parkinson's (PwP). As such there has been much interest in repairing this pathway using transplants of dopamine neurons. This work which began 50 years ago this September is still ongoing and has now moved to first in human trials using human pluripotent stem cell-derived dopaminergic neurons. The results of these trials are eagerly awaited although proof of principle data has already come from trials using human fetal midbrain dopamine cell transplants. This data has shown that developing dopamine cells when transplanted in the brain of a PwP can survive long term with clinical benefits lasting decades and with restoration of normal dopaminergic innervation in the grafted striatum. In this article, we discuss the history of this field and how this has now led us to the recent stem cell trials for PwP.
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| 48. |
- Barker, Roger, et al.
(författare)
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Fetal dopaminergic transplantation trials and the future of neural grafting in Parkinson's disease
- 2013
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Ingår i: Lancet Neurology. - 1474-4465. ; 12:1, s. 84-91
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Forskningsöversikt (refereegranskat)abstract
- Clinical use of allografts of fetal ventral mesencephalic tissue as a treatment to replace dopaminergic neurons in patients with Parkinson's disease was first done more than 20 years ago. Since then, many patients have received transplants, with variable results. During this time, our knowledge of Parkinson's disease has changed and the nature and extent of problems associated with the disorder have been better defined. Our understanding on how best to implement this cell-replacement strategy for patients has grown, but gaining this insight has entailed critical reappraisal of data from transplant trials that have already been undertaken.
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| 49. |
- Barraud, Perrine, et al.
(författare)
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In vitro characterization of a human neural progenitor cell coexpressing SSEA4 and CD133.
- 2007
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 1097-4547 .- 0360-4012. ; 85, s. 250-259
-
Tidskriftsartikel (refereegranskat)abstract
- The stage-specific embryonic antigen 4 (SSEA4) is commonly used as a cell surface marker to identify the pluripotent human embryonic stem (ES) cells. Immunohistochemistry on human embryonic central nervous system revealed that SSEA4 is detectable in the early neuroepithelium, and its expression decreases as development proceeds. Flow cytometry analysis of forebrain-derived cells demonstrated that the SSEA4-expressing cells are enriched in the neural stem/progenitor cell fraction (CD133+), but are rarely codetected with the neural stem cell (NSC) marker CD15. Using a sphere-forming assay, we showed that both subfractions CD133+/SSEA4+ and CD133+/CD15+ isolated from the embryonic forebrain are enriched in neurosphere-initiating cells. In addition CD133, SSEA4, and CD15 expression is sustained in the expanded neurosphere cells and also mark subfractions of neurosphere-initiating cells. Therefore, we propose that SSEA4 associated with CD133 can be used for both the positive selection and the enrichment of neural stem/progenitor cells from human embryonic forebrain.
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| 50. |
- Barraud, Perrine, et al.
(författare)
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Isolation and characterization of neural precursor cells from the Sox1-GFP reporter mouse.
- 2005
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 22:7, s. 1555-1569
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Tidskriftsartikel (refereegranskat)abstract
- We have made use of a reporter mouse line in which enhanced green fluorescence protein (GFP) is inserted into the Sox1 locus. We show that the GFP reporter is coexpressed with the Sox1 protein as well as with other known markers for neural stem and progenitor cells, and can be used to identify and isolate these cells by fluorescence-activated cell sorting (FACS) from the developing or adult brain and from neurosphere cultures. All neurosphere-forming cells with the capacity for multipotency and self-renewal reside in the Sox1–GFP-expressing population. Thus, the Sox1–GFP reporter system is highly useful for identification, isolation and characterization of neural stem and progenitor cells, as well as for the validation of alternative means for isolating neural stem and progenitor cells. Further, transplantation experiments show that Sox1–GFP cells isolated from the foetal brain give rise to neurons and glia in vivo, and that many of the neurons display phenotypic characteristics appropriate for the developing brain region from which the Sox1–GFP precursors were derived. On the other hand, Sox1–GFP cells isolated from the adult subventricular zone or expanded neurosphere cultures gave rise almost exclusively to glial cells following transplantation. Thus, not all Sox1–GFP cells possess the same capacity for neuronal differentiation in vivo.
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