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- Matlik, K, et al.
(author)
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Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 11861-
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Journal article (peer-reviewed)abstract
- Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of dopaminergic neurons in vitro and in vivo. For this reason, GDNF is currently in clinical trials for the treatment of Parkinson’s disease (PD). However, how endogenous GDNF influences dopamine system function and animal behavior is not fully understood. We recently generated GDNF hypermorphic mice that express increased levels of endogenous GDNF from the native locus, resulting in augmented function of the nigrostriatal dopamine system. Specifically, Gdnf wt/hyper mice have a mild increase in striatal and midbrain dopamine levels, increased dopamine transporter activity, and 15% increased numbers of midbrain dopamine neurons and striatal dopaminergic varicosities. Since changes in the dopamine system are implicated in several neuropsychiatric diseases, including schizophrenia, attention deficit hyperactivity disorder (ADHD) and depression, and ectopic GDNF delivery associates with side-effects in PD models and clinical trials, we further investigated Gdnf wt/hyper mice using 20 behavioral tests. Despite increased dopamine levels, dopamine release and dopamine transporter activity, there were no differences in psychiatric disease related phenotypes. However, compared to controls, male Gdnf wt/hyper mice performed better in tests measuring motor function. Therefore, a modest elevation of endogenous GDNF levels improves motor function but does not induce adverse behavioral outcomes.
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- Muller, T., et al.
(author)
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Herschel celestial calibration sources
- 2014
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In: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 37:2, s. 253-330
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Journal article (peer-reviewed)abstract
- Celestial standards play a major role in observational astrophysics. They are needed to characterise the performance of instruments and are paramount for photometric calibration. During the Herschel Calibration Asteroid Preparatory Programme approximately 50 asteroids have been established as far-IR/sub-mm/mm calibrators for Herschel. The selected asteroids fill the flux gap between the sub-mm/mm calibrators Mars, Uranus and Neptune, and the mid-IR bright calibration stars. All three Herschel instruments observed asteroids for various calibration purposes, including pointing tests, absolute flux calibration, relative spectral response function, observing mode validation, and cross-calibration aspects. Here we present newly established models for the four large and well characterized main-belt asteroids (1) Ceres, (2) Pallas, (4) Vesta, and (21) Lutetia which can be considered as new prime flux calibrators. The relevant object-specific properties (size, shape, spin-properties, albedo, thermal properties) are well established. The seasonal (distance to Sun, distance to observer, phase angle, aspect angle) and daily variations (rotation) are included in a new thermophysical model setup for these targets. The thermophysical model predictions agree within 5 % with the available (and independently calibrated) Herschel measurements. The four objects cover the flux regime from just below 1,000 Jy (Ceres at mid-IR N-/Q-band) down to fluxes below 0.1 Jy (Lutetia at the longest wavelengths). Based on the comparison with PACS, SPIRE and HIFI measurements and pre-Herschel experience, the validity of these new prime calibrators ranges from mid-infrared to about 700 mu m, connecting nicely the absolute stellar reference system in the mid-IR with the planet-based calibration at sub-mm/mm wavelengths.
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