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Träfflista för sökning "WFRF:(Bonin Michael) "

Sökning: WFRF:(Bonin Michael)

  • Resultat 1-7 av 7
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1.
  • Siebzehnrübl, Florian A., et al. (författare)
  • Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Acad Sciences. - 0027-8424 .- 1091-6490. ; 115:37, s. 8765-8774
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene (HTT). Although mutant HTT is expressed during embryonic development and throughout life, clinical HD usually manifests later in adulthood. A number of studies document neurodevelopmental changes associated with mutant HTT, but whether these are reversible under therapy remains unclear. Here, we identify very early behavioral, molecular, and cellular changes in preweaning transgenic HD rats and mice. Reduced ultrasonic vocalization, loss of prepulse inhibition, and increased risk taking are accompanied by disturbances of dopaminergic regulation in vivo, reduced neuronal differentiation capacity in subventricular zone stem/progenitor cells, and impaired neuronal and oligodendrocyte differentiation of mouse embryo-derived neural stem cells in vitro. Interventional treatment of this early phenotype with the histone deacetylase inhibitor (HDACi) LBH589 led to significant improvement in behavioral changes and markers of dopaminergic neurotransmission and complete reversal of aberrant neuronal differentiation in vitro and in vivo. Our data support the notion that neurodevelopmental changes contribute to the prodromal phase of HD and that early, presymptomatic intervention using HDACi may represent a promising novel treatment approach for HD.
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2.
  • Bode, Felix J., et al. (författare)
  • Sex differences in a transgenic rat model of Huntington's disease: decreased 17 beta-estradiol levels correlate with reduced numbers of DARPP32(+) neurons in males
  • 2008
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906. ; 17:17, s. 2595-2609
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent clinical studies have highlighted that female sex hormones represent potential neuroprotective mediators against damage caused by acute and chronic brain diseases. This evidence has been confirmed by experimental studies documenting the protective role of female sex hormones both in vitro and in vivo, although these studies did not specifically focus on Huntington's disease (HD). We therefore investigated the onset and course of HD in female and male transgenic (tg) HD (CAG(n51)) and control rats across age and focused on three aspects: (i) behavioral and physiological alterations (energy expenditure, home-cage activity, emotional disturbance and motor dysfunction), (ii) morphological markers (numbers and characteristics of striatal DARPP32(+) medium-sized spiny neurons (MSNs) and dopamine receptor autoradiography) and (iii) peripheral sex hormone levels as well as striatal estrogen receptor expression. Independent of their sex, tgHD rats exhibited increased levels of food intake, elevated home-cage activity scores and anxiolytic-like behavior, whereas only males showed an impairment of motor function. In line with the latter finding, loss and atrophy of DARPP32(+) MSNs were apparent only in male tgHD rats. This result was associated with a decreased striatal dopamine D1 receptor density and lower plasma levels of 17 beta-estradiol at the age of 14 months. As DARPP32(+) MSNs expressed both alpha-and beta-estrogen receptors and showed a correlation between cell numbers and 17 beta-estradiol levels, our findings suggest sex-related differences in the HD phenotype pointing to a substantial neuroprotective effect of sex hormones and opening new perspectives on the therapy of HD.
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3.
  • Freischmidt, Axel, et al. (författare)
  • Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers
  • 2014
  • Ingår i: Brain. - 0006-8950 .- 1460-2156. ; 137:11, s. 2938-2950
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.
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4.
  • Roller-Wirnsberger, Regina, et al. (författare)
  • European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique
  • 2019
  • Ingår i: Age and Ageing. - : Oxford University Press. - 1468-2834. ; 48:2, s. 291-299
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations.Methods: under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators.Results: the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item).Conclusion: the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states.
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5.
  • Johnsson, Filip, et al. (författare)
  • Electricity supply to electric road systems : Impacts on the energy system and environment
  • 2020
  • Rapport (övrigt vetenskapligt)abstract
    • This study analyses how an electrification of the transport sector, including static charging and electric road systems (ERS), could impact the Swedish and German electricity system. The integration of ERS in the electricity system is analysed using: (i) a model-package consisting of an electricity system investment model (ELIN) and electricity system dispatch model (EPOD) and (ii) an energy system investment and dispatch model (SCOPE). The models are run for the same sets of scenarios and methodological differences and results are compared. The modelling results from the CollERS project show that the additional electricity demand from a large-scale implementation of ERS (i.e., a German-Swedish ERS corridor and connecting main road network) is mainly met by investments in wind power in Sweden and both wind and solar power in Germany. Since ERS will take some time to scale up,the modelling shows that there should be enough time for the electricity system to be transformed to meet demand for ERS while also meeting the goals on greenhouse gas reduction.It can be concluded that ERS are increasing the peak power demand (i.e., the net load) in the electricity system. Therefore, there is a need for more investments in peak power units and storage technologies when using ERS. A smart integration of other electricity demand, such as optimisation of the static charging at the home location of passenger cars, can facilitate an efficient use of renewable electricity also with ERS. Thus,it is important that ERS are evaluated and assessed in connection to corresponding assessment of electrification technologies of passenger cars and other sectors, including the industry sector where there are already plans for electrification (e.g. iron and steel, cement and petrochemical industry).The model comparison shows that different assumptions and methodological choices impact what kind of investments are taken, such as in wind, solar and thermal power plants to cover an additional demand from the use of ERS. However, an increase in investments in solar power (Germany) and wind power (Sweden) can be seen in all scenarios to cover the new demand for ERS.
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6.
  • Olovsson, Johanna, 1992, et al. (författare)
  • Impacts of Electric Road Systems on the German and Swedish Electricity Systems—An Energy System Model Comparison
  • 2021
  • Ingår i: Frontiers in Energy Research. - 2296-598X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • This study analyses the impacts of electrification of the transport sector, involving both static charging and electric road systems (ERS), on the Swedish and German electricity systems. The impact on the electricity system of large-scale ERS is investigated by comparing the results from two model packages: 1) a modeling package that consists of an electricity system investment model (ELIN) and electricity system dispatch model (EPOD); and 2) an energy system investment and dispatch model (SCOPE). The same set of scenarios are run for both model packages and the results for ERS are compared. The modeling results show that the additional electricity load arising from large-scale implementation of ERS is mainly, depending on model and scenario, met by investments in wind power in Sweden (40–100%) and in both wind (20–75%) and solar power (40–100%) in Germany. This study also concludes that ERS increase the peak power demand (i.e., the net load) in the electricity system. Therefore, when using ERS, there is a need for additional investments in peak power units and storage technologies to meet this new load. A smart integration of other electricity loads than ERS, such as optimization of static charging at the home location of passenger cars, can facilitate efficient use of renewable electricity also with an electricity system including ERS. A comparison between the results from the different models shows that assumptions and methodological choices dictate which types of investments are made (e.g., wind, solar and thermal power plants) to cover the additional demand for electricity arising from the use of ERS. Nonetheless, both modeling packages yield increases in investments in solar power (Germany) and in wind power (Sweden) in all the scenarios, to cover the new electricity demand for ERS.
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7.
  • Taljegård, Maria, 1988, et al. (författare)
  • Impact of implementation of ERS on the German and Swedish electricity system
  • 2018
  • Konferensbidrag (refereegranskat)abstract
    • The climate benefit from an introduction of Electric Road Systems (ERS) and an increase in the share of electromobility will be determined by the impact on the electricity generation which will be different between countries, depending on the characteristics of the electricity system such as the conditions for renewable electricity. An electrification of the transport sector through electric vehicles (EVs) with static charging and/or ERS introduces a new demand to the electricity system, and hence, will create new load profiles depending on the time of consumption and the amount of electricity used in EVs. Depending on electrification strategy, this new demand may introduce a potential for EVs to provide demand-side management to the power grid. The overall aim of this work is to apply two different electricity systems models to investigate how an electrification of the transport sector could impact the Swedish and German electricity system with respect to energy and power.
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