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  • Hillier, Ladeana W, et al. (författare)
  • Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
  • 2004
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
  • Tidskriftsartikel (refereegranskat)abstract
    • We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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  • Gantner, Carlos W., et al. (författare)
  • Viral Delivery of GDNF Promotes Functional Integration of Human Stem Cell Grafts in Parkinson's Disease
  • 2020
  • Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 26:4, s. 5-526
  • Tidskriftsartikel (refereegranskat)abstract
    • Dopaminergic neurons (DAns), generated from human pluripotent stem cells (hPSCs), are capable of functionally integrating following transplantation and have recently advanced to clinical trials for Parkinson's disease (PD). However, pre-clinical studies have highlighted the low proportion of DAns within hPSC-derived grafts and their inferior plasticity compared to fetal tissue. Here, we examined whether delivery of a developmentally critical protein, glial cell line-derived neurotrophic factor (GDNF), could improve graft outcomes. We tracked the response of DAns implanted into either a GDNF-rich environment or after a delay in exposure. Early GDNF promoted survival and plasticity of non-DAns, leading to enhanced motor recovery in PD rats. Delayed exposure to GDNF promoted functional recovery through increases in DAn specification, DAn plasticity, and DA metabolism. Transcriptional profiling revealed a role for mitogen-activated protein kinase (MAPK)-signaling downstream of GDNF. Collectively, these results demonstrate the potential of neurotrophic gene therapy strategies to improve hPSC graft outcomes.
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  • Hedlund, E, et al. (författare)
  • Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors
  • 2016
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 26448-
  • Tidskriftsartikel (refereegranskat)abstract
    • Degeneration of dopamine neurons in the midbrain causes symptoms of the movement disorder, Parkinson disease. Dopamine neurons are generated from proliferating progenitor cells localized in the embryonic ventral midbrain. However, it remains unclear for how long cells with dopamine progenitor character are retained and if there is any potential for reactivation of such cells after cessation of normal dopamine neurogenesis. We show here that cells expressing Lmx1a and other progenitor markers remain in the midbrain aqueductal zone beyond the major dopamine neurogenic period. These cells express dopamine receptors, are located in regions heavily innervated by midbrain dopamine fibres and their proliferation can be stimulated by antagonizing dopamine receptors, ultimately leading to increased neurogenesis in vivo. Furthermore, treatment with dopamine receptor antagonists enhances neurogenesis in vitro, both from embryonic midbrain progenitors as well as from embryonic stem cells. Altogether our results indicate a potential for reactivation of resident midbrain cells with dopamine progenitor potential beyond the normal period of dopamine neurogenesis.
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  • Hollnagel, Erik, et al. (författare)
  • Principles for modelling function allocation
  • 2000
  • Ingår i: International journal of human-computer studies. - : Elsevier BV. - 1071-5819 .- 1095-9300. ; 52:2, s. 253-265
  • Tidskriftsartikel (refereegranskat)abstract
    • Automation is the key element in safety, reliability of industrial processes. Selecting the right type and level of automation requires careful consideration of how to allocate tasks between operators and automation. This is important in order that the joint system, human and machine as seen together, perform in the intended manner. The Halden Reactor Project is currently engaged in a project to study this topic, with an emphasis on maximizing the operator's ability to maintain control and handle unexpected events. Functional models can be used to study this in a process control environment, because they explicitly describe the functions that must be provided by the process or the operator. This paper describes how functional modelling of the joint system can be used to provide a basis for how functions should be allocated.
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