Cholinergic-rich brain transplants reverse alcohol-induced memory deficits

Alcohol-induced memory impairment in man has been attributed to deficiencies in subcortical noradrenergic and cholinergic systems, as well as to damage in midbrain structures. Korsakoff's psychosis, a disease in which alcohol poisoning causes apparently irreversible memory defects, is characterized by lesions in cholinergic and noradrenergic nuclei and by a decrease in the activity of choline acetyltransferase (ChAT) and the content of noradrenaline (NA) in forebrain areas such as cerebral cortex and hippocampus, innervated by these nuclei. Prolonged intake of ethanol in rodents similarly produces signs of noradrenergic and cholinergic deafferentation in the cortex and hippocampus, as well as persistent memory deficits. To test whether alcohol-induced memory impairments depend on cholinergic deafferentation, we transplanted cholinergic-rich fetal basal forebrain cell suspensions into the cortex and hippocampus of alcohol-treated rats. The substantial and persistent memory losses produced in our rats by ethanol intake were associated with an impairment of cholinergic function, and were reversed by cholinergic-rich transplants into cortex and hippocampus.     

New Amphenone analogs as adrenocortical inhibitors

Zusammenfassung 2-Methyl-1,2-bis-(3-pyridyl)-1-propanon (Su 4885) hemmt beim Hund die Ausscheidung von 17-OH-Steroiden aus den Nebennieren und hemmtin vitro ähnlich wie Amphenon den ACTH-Effekt auf Ratten-, Meerschweinchen-und Hunde-Nebennieren.In situ bei der Ratte hat es jedoch keine Amphenon-Wirkung, von dem es sich auch sonst unterscheidet.     

Thermochemical structures beneath Africa and the Pacific Ocean

Large low-velocity seismic anomalies have been detected in the Earth's lower mantle beneath Africa and the Pacific Ocean that are not easily explained by temperature variations alone. The African anomaly has been interpreted to be a northwest-southeast-trending structure with a sharp-edged linear, ridge-like morphology. The Pacific anomaly, on the other hand, appears to be more rounded in shape. Mantle models with heterogeneous composition have related these structures to dense thermochemical piles or superplumes. It has not been shown, however, that such models can lead to thermochemical structures that satisfy the geometrical constraints, as inferred from seismological observations. Here we present numerical models of thermochemical convection in a three-dimensional spherical geometry using plate velocities inferred for the past 119 million years. We show that Earth's subduction history can lead to thermochemical structures similar in shape to the observed large, lower-mantle velocity anomalies. We find that subduction history tends to focus dense material into a ridge-like pile beneath Africa and a relatively more-rounded pile under the Pacific Ocean, consistent with seismic observations.     

Gene network shaping of inherent noise spectra

Recent work demonstrates that stochastic fluctuations in molecular populations have consequences for gene regulation. Previous experiments focused on noise sources or noise propagation through gene networks by measuring noise magnitudes. However, in theoretical analysis, we showed that noise frequency content is determined by the underlying gene circuits, leading to a mapping between gene circuit structure and the noise frequency range. An intriguing prediction from our previous studies was that negative autoregulation shifts noise to higher frequencies where it is more easily filtered out by gene networks--a property that may contribute to the prevalence of autoregulation motifs (for example, found in the regulation of approximately 40% of Escherichia coli genes). Here we measure noise frequency content in growing cultures of E. coli, and verify the link between gene circuit structure and noise spectra by demonstrating the negative autoregulation-mediated spectral shift. We further demonstrate that noise spectral measurements provide mechanistic insights into gene regulation, as perturbations of gene circuit parameters are discernible in the measured noise frequency ranges. These results suggest that noise spectral measurements could facilitate the discovery of novel regulatory relationships.