Showing papers by "Anders Björklund published in 2010"
TL;DR: In this paper, the authors summarize and evaluate recent empirical research on education and family background, focusing on two related but distinct motivations for this topic: equality of opportunity and the child development perspective.
Abstract: In every society for which we have data, people’s educational achievement is positively correlated with their parents’ education or with other indicators of their parents’ socioeconomic status. This topic is central in social science, and there is no doubt that research has intensified during recent decades, not least thanks to better data having become accessible to researchers. The purpose of this chapter is to summarize and evaluate recent empirical research on education and family background. Broadly speaking, we focus on two related but distinct motivations for this topic. The first is equality of opportunity. Here, major the research issues are: How important a determinant of educational attainment is family background, and is family background – in the broad sense that incorporates factors not chosen by the individual – a major, or only a minor, determinant of educational attainment? What are the mechanisms that make family background important? Have specific policy reforms been successful in reducing the impact of family background on educational achievement? The second common starting point for recent research has been the child development perspective. Here, the focus is on how human-capital accumulation is affected by early childhood resources. Studies with this focus address the questions: what types of parental resources or inputs are important for children’s development, why are they important and when are they important? In addition, this literature focuses on exploring which types of economic policy, and what timing of the policy in relation to children’s social and cognitive development, are conducive to children’s performance and adult outcomes. The policy interest in this research is whether policies that change parents’ resources and restrictions have causal effects on their children.
332 citations
TL;DR: Two patients with Parkinson’s disease, successfully treated with fetal tissue transplants more than a decade ago, developed troublesome involuntary movements, which were determined to be a result of an overabundance of serotonin-using neurons that developed from the graft, and strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease are suggested.
Abstract: Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by L-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated by systemic administration of a serotonin [5-hydroxytryptamine (5-HT)] receptor (5-HT1A) agonist, which dampens transmitter release from serotonergic neurons, indicating that the dyskinesias were caused by the serotonergic hyperinnervation. Our observations suggest strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease with fetal tissue or stem cells.
288 citations
TL;DR: The data indicate that Lewy bodies develop gradually in transplanted dopaminergic neurons in a fashion similar to that in dopamine neurons in the host substantia nigra.
Abstract: We previously reported the occurrence of Lewy bodies in grafted human fetal mesencephalic neurons in two patients with Parkinson's disease. Here, we have used immunohistochemistry and electron microscopy to characterize the development of Lewy bodies in one of these cases. This patient was operated in putamen on both sides at 12 or 16 years before death, respectively. We demonstrate that 2% of the 12-year-old and 5% of the 16-year-old grafted, presumed dopaminergic neurons contained Lewy bodies immunoreactive for alpha-synuclein. Based on morphological analysis, two forms of alpha-synuclein-positive aggregates were distinguished in the grafts, the first a classical and compact Lewy body, the other a loose meshwork aggregate. Lewy bodies in the grafts stained positively for ubiquitin and thioflavin-S, and contained characteristic alpha-synuclein immunoreactive electron dense fibrillar structures on electron microscopy. Our data indicate that Lewy bodies develop gradually in transplanted dopaminergic neurons in a fashion similar to that in dopaminergic neurons in the host substantia nigra.
199 citations
TL;DR: It is found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug‐induced rotation tests, can be used to select animals with profound dopamine lesions that are stable over time.
Abstract: Despite the widespread use of mice as models of Parkinson’s disease there is a surprising lack of validation and characterisation of unilateral lesion models in mice and the extent of behavioural impairments induced by such lesions. The aim of the present study was to characterise the behavioural deficits observed after injection of 6-hydroxydopamine unilaterally into the substantia nigra, and correlate the behavioural impairments with the extent of damage to the mesostriatal dopaminergic pathway. We found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug-induced rotation tests, can be used to select animals with profound (‡ 80%) dopaminergic lesions that are stable over time. Based on these data we propose criteria that can be used to predict the extent of lesion, classified as severe, intermediate or mild lesions of the mesostriatal pathway. The correlation of cell loss and striatal innervation with the performance in each test provides a useful tool for the assessment of functional recovery in neurorestoration and cell transplantation studies, and for the evaluation of the in vivo efficacy and performance of stem cell-derived dopamine neuron preparations.
133 citations
TL;DR: The results show that the A9 component of intrastriatal grafts is of critical importance for recovery in tests on motor performance, in a rodent model of Parkinson’s disease.
Abstract: Grafts of foetal ventral mesencephalon, used in cell replacement therapy for Parkinson’s disease, are known to contain a mix of dopamine neuronal subtypes including the A9 neurons of the substantia nigra and the A10 neurons of the ventral tegmental area. However, the relative importance of these subtypes for functional repair of the brain affected by Parkinson’s disease has not been studied thoroughly. Here, we report results from a series of grafting experiments where the anatomical and functional properties of grafts either selectively lacking in A9 neurons, or with a typical A9/A10 composition were compared. The results show that the A9 component of intrastriatal grafts is of critical importance for recovery in tests on motor performance, in a rodent model of Parkinson’s disease. Analysis at the histological level indicates that this is likely to be due to the unique ability of A9 neurons to innervate and functionally activate their target structure, the dorsolateral region of the host striatum. The findings highlight dopamine neuronal subtype composition as a potentially important parameter to monitor in order to understand the variable nature of functional outcome better in transplantation studies. Furthermore, the results have interesting implications for current efforts in this field to generate well-characterized and standardized preparations of transplantable dopamine neuronal progenitors from stem cells.
129 citations
TL;DR: Targeted overexpression of human α-synuclein in midbrain dopamine neurons, using AAV vectors, reproduces many of the characteristic features of the human disease and provides, for the first time, a model of progressive PD that can be applied to both rodents and primates.
Abstract: The discovery of the role of α-synuclein in the pathogenesis of Parkinson's disease (PD) has opened new possibilities for the development of more authentic models of Parkinson's disease. Recombinant adeno-associated virus (AAV) and lentivirus (LV) vectors are efficient tools for expression of genes locally in subsets of neurons in the brain and can be used to express human wild-type or mutated α-synuclein selectively in midbrain dopamine neurons. Using this approach, it is possible to trigger extensive PD-like cellular and axonal pathologies in the nigrostriatal projection, involving abnormal protein aggregation, neuronal dysfunction, and cell death that develop progressively over time. Targeted overexpression of human α-synuclein in midbrain dopamine neurons, using AAV vectors, reproduces many of the characteristic features of the human disease and provides, for the first time, a model of progressive PD that can be applied to both rodents and primates.
104 citations
TL;DR: The authors employ a data set with rich family information to explore what factors in addition to traditional measures of parents' socio-economic status can explain sibling similarity in long-run income and find that more than half of the family and community influences that siblings share are uncorrelated with parental income.
Abstract: Sibling correlations are broader measures of the impact of family and community influences on individual outcomes than intergenerational correlations. Estimates of such correlations in income show that more than half of the family and community influences that siblings share are uncorrelated with parental income. We employ a data set with rich family information to explore what factors in addition to traditional measures of parents' socio-economic status can explain sibling similarity in long-run income. Measures of family structure and social problems account for very little of sibling similarities beyond that already accounted for by income, education and occupation. However, when we add indicators of parental involvement in schoolwork, parenting practices and maternal attitudes, the explanatory power of our variables increases from about one-quarter (using only traditional measures of parents' socio-economic status) to nearly two-thirds.
98 citations
TL;DR: For the purpose of understanding the underlying mechanisms behind intergenerational associations in income and education, recent studies have explored the inter-generational transmission of abilitie... as mentioned in this paper.
Abstract: For the purpose of understanding the underlying mechanisms behind intergenerational associations in income and education, recent studies have explored the intergenerational transmission of abilitie ...
79 citations
TL;DR: This work has shown that dopamine released from spared serotonin afferents can act as a trigger of dyskinetic movements induced by repetitive, low doses of levodopa, and this mechanism may also play a role in the development of graft‐induced dyskinesias in patients that receive fetal neuron transplants.
Abstract: Recent studies in animal models of Parkinson's disease (PD) have provided evidence that dopamine released from spared serotonin afferents can act as a trigger of dyskinetic movements induced by repetitive, low doses of levodopa. Serotonin neurons have the capacity to store and release dopamine synthesized from systemically administered levodopa. However, because of the lack of any autoregulatory feedback control, dopamine released from serotonin terminals results in excessive swings in extracellular dopamine levels after peripheral administration of levodopa. Such "dysregulated" release of levodopa-derived dopamine is likely to be responsible for the appearance of the abnormal movements in levodopa-primed animals. This mechanism may also play a role in the development of graft-induced dyskinesias in patients that receive fetal neuron transplants, possibly due to the inclusion of serotonin neurons in the grafted ventral midbrain tissue, which contribute to maintain dopamine receptors of the denervated striatum in a supersensitive state.
68 citations
TL;DR: Based on the available clinical and preclinical data, strategies to avoid GID in future clinical trials using fetal cell transplants or cell preparations derived from stem cells are outlined.
Abstract: The development of neural transplantation as a treatment for Parkinson’s disease has been compromised by a lack of functional efficacy and the appearance of transplant-induced motor side-effects in some patients. Since the first reports of these graft-induced dyskinesias (GID), and the realization of their impact on the progress of the field, a great deal of experimental work has been performed to determine the underlying cause(s) of this problematic side-effect. In this review we describe the clinical phenomenon of GID, explore the different representations of GID in rodent models, and examine the various hypotheses that have been postulated to be the cause. Based on the available clinical and preclinical data we outline strategies to avoid GID in future clinical trials using fetal cell transplants or cell preparations derived from stem cells.
61 citations
TL;DR: A microRNA-regulated lentiviral reporter system was used to visualize and segregate differentiating neuronal cells in pluripotent cultures and track progeny from murine ES, human ES cells, and induced plurIPotent stem cells as they differentiated toward the neural lineage.
Abstract: In this study, we have used a microRNA-regulated lentiviral reporter system to visualize and segregate differentiating neuronal cells in pluripotent cultures. Efficient suppression of transgene expression, specifically in undifferentiated pluripotent cells, was achieved by using a lentiviral vector expressing a fluorescent reporter gene regulated by microRNA-292. Using this strategy, it was possible to track progeny from murine ES, human ES cells, and induced pluripotent stem cells as they differentiated toward the neural lineage. In addition, this strategy was successfully used to FACS purify neuronal progenitors for molecular analysis and transplantation. FACS enrichment reduced tumor formation and increased survival of ES cell-derived neuronal progenitors after transplantation. The properties and versatility of the microRNA-regulated vectors allows broad use of these vectors in stem cell applications.
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TL;DR: In this article, the authors summarize and evaluate recent empirical research on education and family background, focusing on two related but distinct motivations for this topic: equality of opportunity and the child development perspective.
Abstract: In every society for which we have data, people’s educational achievement is positively correlated with their parents’ education or with other indicators of their parents’ socioeconomic status. This topic is central in social science, and there is no doubt that research has intensified during recent decades, not least thanks to better data having become accessible to researchers. The purpose of this chapter is to summarize and evaluate recent empirical research on education and family background. Broadly speaking, we focus on two related but distinct motivations for this topic. The first is equality of opportunity. Here, major the research issues are: How important a determinant of educational attainment is family background, and is family background – in the broad sense that incorporates factors not chosen by the individual – a major, or only a minor, determinant of educational attainment? What are the mechanisms that make family background important? Have specific policy reforms been successful in reducing the impact of family background on educational achievement? The second common starting point for recent research has been the child development perspective. Here, the focus is on how human-capital accumulation is affected by early childhood resources. Studies with this focus address the questions: what types of parental resources or inputs are important for children's development, why are they important and when are they important? In addition, this literature focuses on exploring which types of economic policy, and what timing of the policy in relation to children's social and cognitive development, are conducive to children's performance and adult outcomes. The policy interest in this research is whether policies that change parents' resources and restrictions have causal effects on their children.
01 Jan 2010
TL;DR: In this paper, Huvudfragan et al. present a rapport with Vilka arbetsmarknadseffekter har svensk utbildningspolitik.
Abstract: Avsevarda resurser laggs pa utbildning i alla OECD lander. Sverige ar inget undantag: De direkta utbildningsutgifterna utgjorde 6,3 % av BNP 2006, vilket kan jamforas med 5,7 % som genomsnitt i OECD vid samma tidpunkt (OECD 2009). Vilka intakter generar da dessa utgifter? Ett viktigt motiv for utbildningsinsatserna ar att forbattra individers kunskaper vilket i sin tur ska hoja deras produktivitet och forbattra deras sysselsattningsmojligheter, nagot som okar den samlade produktionen i landet. Syftet med denna rapport ar att undersoka om utbildningsinsatser har sadana effekter for den enskilde individen. Huvudfragan i rapporten ar: Vilka arbetsmarknadseffekter har svensk utbildningspolitik? Med ”arbetsmarknadseffekter” menar vi huvudsakligen effekter pa individers loner, sysselsattning och arbetsinkomster. Men vi kommer ocksa att studera utfall som betyg och testresultat.
TL;DR: It is demonstrated that GLI1 is a determinant of FP specification in hESC and a highly robust and efficient in vitro model system that mimics the ventral neural tube organizer is described.
Abstract: Generation of mesencephalic dopamine (mesDA) neurons from human embryonic stem cells (hESCs) requires several stages of signaling from various extrinsic and intrinsic factors. To date, most methods incorporate exogenous treatment of Sonic hedgehog (SHH) to derive mesDA neurons. However, we and others have shown that this approach is inefficient for generating FOXA2+ cells, the precursors of mesDA neurons. As mesDA neurons are derived from the ventral floor plate (FP) regions of the embryonic neural tube, we sought to develop a system to derive FP cells from hESC. We show that forced expression of the transcription factor GLI1 in hESC at the earliest stage of neural induction, resulted in their commitment to FP lineage. The GLI1+ cells coexpressed FP markers, FOXA2 and Corin, and displayed exocrine SHH activity by ventrally patterning the surrounding neural progenitors. This system results in 63% FOXA2+ cells at the neural progenitor stage of hESC differentiation. The GLI1-transduced cells were also able to differentiate to neurons expressing tyrosine hydroxylase. This study demonstrates that GLI1 is a determinant of FP specification in hESC and describes a highly robust and efficient in vitro model system that mimics the ventral neural tube organizer.
Patent•
09 Nov 2010
TL;DR: In this paper, a one-vector expression system comprising a sequence encoding two polypeptides, such as tyrosine hydroxylase (TH) and GTP-cyclohydrolase 1 (GCH1), was proposed.
Abstract: The present invention relates to a one-vector expression system comprising a sequence encoding two polypeptides, such as tyrosine hydroxylase (TH) and GTP-cyclohydrolase 1 (GCH1). The two polypeptides can be should preferentially be expressed at a ratio between 3:1 and 15:1, such as between 3:1 and 7:1. The invention is useful in the treatment of catecholamine deficient disorders, such as dopamine deficient disorders including but not limited to Parkinson's Disease. Moreover, the present invention provides a method to deliver the vector construct in order to limit the increased production of the catecholamine to the cells in need thereof.
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TL;DR: This paper found that intergenerational transmission is very strong in the top of the income distribution, more so for income than for earnings, and that wealth is the most likely channel to explain this strong transmission.
Abstract: This paper presents new evidence on intergenerational mobility in the top of the income and earnings distribution. Using a large dataset of matched father-son pairs in Sweden, we find that intergenerational transmission is very strong in the top, more so for income than for earnings. In the extreme top (top 0.1 percent) income transmission is remarkable with an IG elasticity above 0.9. We also study potential transmission mechanisms and find that sons’ IQ, non-cognitive skills and education are all unlikely channels in explaining this strong transmission. Within the top percentile, increases in fathers’ income are, if anything, negatively associated with these variables. Wealth, on the other hand, has a significantly positive association. Our results suggest that Sweden, known for having relatively high intergenerational mobility in general, is a society where transmission remains strong in the very top of the distribution and that wealth is the most likely channel.
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TL;DR: In this paper, the authors examined whether parental marriage confers educational advantages to children relative to cohabitation, and they exploited a dramatic marriage boom in Sweden in late 1989 created by a reform of...
Abstract: This paper examines whether parental marriage confers educational advantages to children relative to cohabitation. We exploit a dramatic marriage boom in Sweden in late 1989 created by a reform of ...
Journal Article•
Patent•
09 Nov 2010
TL;DR: In this paper, a one-vector expression system comprising a sequence encoding two polypeptides, such as tyrosine hydroxylase (TH) and GTP-cyclohydrolase 1 (GCH1), was proposed.
Abstract: The present invention relates to a one-vector expression system comprising a sequence encoding two polypeptides, such as tyrosine hydroxylase (TH) and GTP- cyclohydrolase 1 (GCH1 ). The two polypeptides can be should preferentially be expressed at a ratio between 3:1 and 15:1, such as between 3:1 and 7:1. The invention is useful in the treatment of catecholamine deficient disorders, such as dopamine deficient disorders including but not limited to Parkinson's Disease. Moreover, the present invention provides a method to deliver the vector construct in order to limit the increased production of the catecholamine to the cells in need thereof.