The transgenic embryos express green fluorescent protein (GFP) localized in the motor neurons
making them ideal for evaluating motor neuron development and toxicities in vivo. The hb9:GFP zebrafish embryos (28 h post fertilization) treated with 2 mM ketamine for learn more 20 h demonstrated significant reductions in spinal motor neuron numbers, while co-treatment with acetyl L-carnitine proved to be neuroprotective. In whole mount immunohistochemical studies using WT embryos, a similar effect was observed for the primary sensory neurons. In the ketamine-treated WT embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced compared to that in controls. However, acetyl L-carnitine co-treatment prevented ketamine-induced adverse effects on the RB neurons. These
results suggest that acetyl L-camitine protects both motor and sensory neurons from ketamine-induced neurotoxicity. Published by Elsevier Inc.”
“The solution dynamics of an enzyme acid-beta-glucocerebrosidase Palbociclib (GCase) probed at a physiologically relevant (lysosomal) pH by hydrogen/deuterium exchange mass spectrometry (HDX-MS) reveals very uneven distribution of backbone amide protection across the polypeptide chain Highly mobile segments are observed even within the catalytic cavity alongside highly protective segments, highlighting the importance of the balance between conformational stability and flexibility for enzymatic activity Forced oxidation of GCase that resulted in a 40-60% reduction in in vitro biological activity affects the stability of some key structural elements within the catalytic site These changes in dynamics occur on a longer time scale that is irrelevant for catalysis, effectively ruling out loss of structure in the catalytic site as a major factor contributing to the reduction of the catalytic activity Oxidation also leads to noticeable destabilization of conformation in remote protein segments on a much larger scale, which is likely to increase the aggregation propensity of GCase and affect its bioavailability
Therefore, it appears that oxidation exerts its negative impact on the biological activity of GCase indirectly, over primarily through accelerated aggregation and impaired trafficking”
“Animal model-based studies have shown that ethanol exposure during early gestation induces developmental stage-specific abnormalities of the face and brain. The exposure time-dependent variability in ethanol’s teratogenic outcomes is expected to contribute significantly to the wide spectrum of effects observed in humans with fetal alcohol spectrum disorder (FASD). The work presented here employs a mouse FASD model and magnetic resonance microscopy (MRM; high resolution magnetic resonance imaging) in studies designed to further our understanding of the developmental stage-specific defects of the brain that are induced by ethanol. At neurulation stages, i.e.