Results of correlation of values of individual behaviour of rats with liver tryptophan pyrrolase activity.

A significant negative correlation was found between the individual animal's horizontal activity in an open field and liver tryptophan pyrrolase (LTP) activity. On the other hand, the duration of immobility in an open field correlated postively and significantly with liver tryptophan pyrrolase activity.     

Interrelationships between hydrogen-supplying reactions, respiration rate and extramitochondrial adenine nucleotide pattern

1. The influence of a diminished hydrogen supply on the regulation of oxidative phosphorylation of isolated rat liver mitochondria in dependence on the extramitochondrial (ATP)/(ADP) ratio was investigated. 2. The hydrogen supply was diminished by using various (beta-hydroxybutyrate)/(acetoacetate) ratios as a redox buffer and the results were compared with those of experiments using perifusion of immobilized mitochondria with non-saturating substrate concentrations. 3. In both experimental approaches the influence of a diminished hydrogen pressure on the maximum (ATP)/(ADP) ratio at minimum flux was low. An extreme decrease in the (beta-hydroxybutyrate)/(acetoacetate) ratio by more than two orders of magnetitude causes the (APT)/(ADP) ratio to decrease by about 50%. 4. The load capacity of oxidative phosphorylation (maximum flux) is considerably decreased by diminished hydrogen pressure. 5. The borderline cases of purely kinetic and thermodynamic limitations of hydrogen supply were calculated by computer simulation with respect to the regulating behaviour of oxidative phosphorylation and changes in the control strength of adenine nucleotide translocator and hydrogen supply in the overall reaction. 6. A prevalent thermodynamic influence of hydrogen supply on oxidative energy transformation in the cell is discussed in the light of experimental data.     

Unprecedented Therapeutic Potential with a Combination of A2A/NR2B Receptor Antagonists as Observed in the 6-OHDA Lesioned Rat Model of Parkinson's Disease

In Parkinson''s disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A_2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261+ Merck 22; Sch-58261+Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug separately and to determine whether any interaction between two drugs was additive or synergistic. Additional post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered separately at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacological interactions. The combined administration of A_2A/NR2B-receptor antagonists improved motor behaviour in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients.     

Diverse phylogeny and morphology of magnetite biomineralized by magnetotactic cocci

Magnetotactic bacteria (MTB) are diverse prokaryotes that produce magnetic nanocrystals within intracellular membranes (magnetosomes). Here, we present a large-scale analysis of diversity and magnetosome biomineralization in modern magnetotactic cocci, which are the most abundant MTB morphotypes in nature. Nineteen novel magnetotactic cocci species are identified phylogenetically and structurally at the single-cell level. Phylogenetic analysis demonstrates that the cocci cluster into an independent branch from other Alphaproteobacteria MTB, that is, within the Etaproteobacteria class in the Proteobacteria phylum. Statistical analysis reveals species-specific biomineralization of magnetosomal magnetite morphologies. This further confirms that magnetosome biomineralization is controlled strictly by the MTB cell and differs among species or strains. The post-mortem remains of MTB are often preserved as magnetofossils within sediments or sedimentary rocks, yet paleobiological and geological interpretation of their fossil record remains challenging. Our results indicate that magnetofossil morphology could be a promising proxy for retrieving paleobiological information about ancient MTB.     

Early-Life Hepatitis E Infection in Pigs: The Importance of Maternally-Derived Antibodies

Passive immunity (PI), acquired through colostrum intake, is essential for piglet protection against pathogens. Maternally-derived antibodies (MDAs) can decrease the transmission of pathogens between individuals by reducing shedding from infected animals and/or susceptibility of naïve animals. Only a limited number of studies, however, have been carried out to quantify the level of protection conferred by PI in terms of transmission. In the present study, an original modeling framework was designed to estimate parameters governing the transmission of infectious agents in the presence and absence of PI. This epidemiological model accounts for the distribution of PI duration and two different forces of infection depending on the serological status of animals after colostrum intake. A Bayesian approach (Metropolis-Hastings algorithm) was used for parameter estimation. The impact of PI on hepatitis E virus transmission in piglets was investigated using longitudinal serological data from six pig farms. A strong impact of PI was highlighted, the efficiency of transmission being on average 13 times lower in piglets with maternally-derived antibodies than in fully susceptible animals (range: 5–21). Median infection-free survival ages, based on herd-specific estimates, ranged between 8.7 and 13.8 weeks in all but one herd. Indeed, this herd exhibited a different profile with a relatively low prevalence of infected pigs (50% at slaughter age) despite the similar proportions of passively immune individuals after colostrum intake. These results suggest that the age at HEV infection is not strictly dependent upon the proportion of piglets with PI but is also linked to farm-specific husbandry (mingling of piglets after weaning) and hygiene practices. The original methodology developed here, using population-based longitudinal serological data, was able to demonstrate the relative impact of MDAs on the transmission of infectious agents.