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- Wallen-Mackenzie, A, et al.
(author)
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Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells
- 2003
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In: Genes & development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 17:24, s. 3036-3047
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Journal article (peer-reviewed)abstract
- The retinoid X receptor (RXR) is essential as a common heterodimerization partner of several nuclear receptors (NRs). However, its function as a bona fide receptor for endogenous ligands has remained poorly understood. Such a role would depend on the existence of RXR activating ligands in vivo and on the ability of such ligands to influence relevant biological functions. Here we demonstrate the presence of endogenous RXR ligands in the embryonic central nervous system (CNS) and show that they can activate heterodimers formed between RXR and the orphan NR Nurr1 in vivo. Moreover, RXR ligands increase the number of surviving dopaminergic cells and other neurons in a process mediated by Nurr1-RXR heterodimers. These results provide evidence for a role of Nurr1 as a ligand-independent partner of RXR in its function as a bona fide ligand-activated NR. Finally, our findings identify RXR-Nurr1 heterodimers as a potential target in the treatment of neurodegenerative disease.
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- Cangiano, L, et al.
(author)
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Role of apamin-sensitive k(ca) channels for reticulospinal synaptic transmission to motoneuron and for the afterhyperpolarization
- 2002
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In: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 88:1, s. 289-299
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Journal article (peer-reviewed)abstract
- Single motoneurons and pairs of a presynaptic reticulospinal axon and a postsynaptic motoneuron were recorded in the isolated lamprey spinal cord, to investigate the role of calcium-dependent K+ channels (KCa) during the afterhyperpolarization following the action potential (AHP), and glutamatergic synaptic transmission on the dendritic level. The AHP consists of a fast phase due to transient K+ channels (fAHP) and a slower phase lasting 100–200 ms (sAHP), being the main determinant of spike frequency regulation. We now present evidence that the sAHP has two components. The larger part, around 80%, is abolished by superfusion of Cd2+ (blocker of voltage-dependent Ca2+ channels), by intracellular injection of 1,2-bis-( 2-aminophenoxy)-ethane- N,N,N′,N′-tetraacetic acid (BAPTA; fast Ca2+ chelator), and by apamin (selective toxin for KCa channels of the SK subtype). While 80% of the sAHP is thus due to KCa channels, the remaining 20% is not mediated by Ca2+, either entering through voltage-dependent Ca2+ channels or released from intracellular Ca2+ stores. This Ca2+-independent sAHP component has a similar time course as the KCa portion and is not due to a Cl− conductance. It may be caused by Na+-activated K+ channels. Glutamatergic excitatory postsynaptic potentials (EPSPs) evoked by single reticulospinal axons give rise to a local Ca2+ increase in the postsynaptic dendrite, mediated in part by N-methyl-d-aspartate (NMDA) receptors. The Ca2+ levels remain elevated for several hundred milliseconds and could be expected to activate KCa channels. If so, this activation should cause a local conductance increase in the dendrite that would shunt EPSPs following the first EPSP in a spike train. We have tested this in reticulospinal/motoneuronal pairs, by stimulating the presynaptic axon with spike trains at different frequencies. We compared the first EPSP and the following EPSPs in the control and after blockade with apamin. No difference was observed in EPSP amplitude or shape before and after apamin, either in normal Ringer or in Mg2+-free Ringer removing the voltage-dependent block of NMDA receptors. In conclusion, the local Ca2+ entry during reticulospinal EPSPs does not cause an activation of KCa channels sufficient to affect the efficacy of synaptic transmission. Thus the integration of synaptic signals at the dendritic level in motoneurons appears simpler than would otherwise have been the case.
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- Eriksson, Mikael, et al.
(author)
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MAX4, a 3 GeV light source with a flexible injector
- 2002
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In: 8th European Particle Accelerator Conference. ; , s. 686-687
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Conference paper (peer-reviewed)abstract
- The MAX4 ring is intended to be the future user facility at MAXlab. The high-brilliance 3 GeV storage ring, equipped with small gap, short period superconducting undulators, demonstrates a high mean brilliance over a wide photon energy spectrum. The ring itself is defined from the routine operation of the small gap insertion devices, which is reflected in the small aperture of the ring magnets. The development of future light sources, like the free electron laser and energy recovery systems, opens up new challenging possibilities to create high brilliance, short pulse radiation. This development is today far from being mature, a strong development of new ideas and techniques will most probably take place during the next decade(s). The MAX4 full-energy injector is constructed to incorporate these future developments. The proposed 3 GeV energy recovery race-track microtron will open up the possibility of topping up injection and to deliver Fourier transform limited spontaneous as well as coherent radiation up to the hard X-ray spectral region
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