Joint explorative analysis of neuroreceptor subsystems in the human brain: application to receptor-transporter correlation using PET data

Positron emission tomography (PET) has proved to be a highly successful technique in the qualitative and quantitative exploration of the human brain's neurotransmitter-receptor systems. In recent years, the number of PET radioligands, targeted to different neuroreceptor systems of the human brain, has increased considerably. This development paves the way for a simultaneous analysis of different receptor systems and subsystems in the same individual. The detailed exploration of the versatility of neuroreceptor systems requires novel technical approaches, capable of operating on huge parametric image datasets. An initial step of such explorative data processing and analysis should be the development of novel exploratory data-mining tools to gain insight into the "structure" of complex multi-individual, multi-receptor data sets. For practical reasons, a possible and feasible starting point of multi-receptor research can be the analysis of the pre- and post-synaptic binding sites of the same neurotransmitter. In the present study, we propose an unsupervised, unbiased data-mining tool for this task and demonstrate its usefulness by using quantitative receptor maps, obtained with positron emission tomography, from five healthy subjects on (pre-synaptic) serotonin transporters (5-HTT or SERT) and (post-synaptic) 5-HT(1A) receptors. Major components of the proposed technique include the projection of the input receptor maps to a feature space, the quasi-clustering and classification of projected data (neighbourhood formation), trans-individual analysis of neighbourhood properties (trajectory analysis), and the back-projection of the results of trajectory analysis to normal space (creation of multi-receptor maps). The resulting multi-receptor maps suggest that complex relationships and tendencies in the relationship between pre- and post-synaptic transporter-receptor systems can be revealed and classified by using this method. As an example, we demonstrate the regional correlation of the serotonin transporter-receptor systems. These parameter-specific multi-receptor maps can usefully guide the researchers in their endeavour to formulate models of multi-receptor interactions and changes in the human brain.     

On the physics of the symbol--matter problem in biological systems and the origin of life: affine Hilbert spaces model of the robustness of the internal quantum dynamics of biological systems

In the present paper, some physical considerations of the biological symbol-matter problem is exposed. First of all, the physical concept of quantum dynamical internal measuremental robustness is discussed. In this context, the significance of introducing affine molecular Hilbert spaces, the original (primordeal) internal quantum measurement, and the global constraining nature of time-inversion symmetry restoring, as a special restoration force, is discussed at some length. It is pointed out, as a summary, that global robustness of the internal dynamics of quantum measurements is due to two basic factors: on one hand, the global constraining nature of the chosen specific (symmetry-) restoring force, and on the other, the individual robustness of the discrete local internal measuremental interactions. The second condition is supposed to follow from a system-internalised ("objective") Bohr-type Copenhagen interpretation of quantum mechanics, corresponding, in an external context, to the Generalized Complementarity Principle of Bohr and Elsasser. It is not claimed, however, that this latter problem has been, as yet, satisfactorily settled physically. In fact, if it were, it would amount to a specifically biological quantum theory of internal measurement, which had to be rooted in the original primordeal global internal measurement, amounting to the origin of the genetic code.     

Organization of work via a natural substance: regulation of nest construction in social wasps

In social insects, colony-level complexity emerges from simple individual-level behaviors and interactions. In the evolution of insect societies, selection has acted to promote efficiency through division of labor. Nest construction of social wasps is an excellent model system to study division of labor and the performance of a decentralized behavioral regulation. After re-examination of Jeanne's (1996) demand-driven "non-taskmates feedback" hypothesis, an alternative mechanism is suggested whereby the regulation of behavior is based on a natural substance (water) which is itself also a building material. By experimenting with a simple model system, we show that the model's predictions agree with observational data and cover a wide range of evolutionary transitions. According to the internal and external parameters, the colony builds up storage of water that is used both as regulator and building material. Through individual interactions, pulp foragers and water foragers emerge from general laborers and their ratio becomes balanced. The emergent foragers ensure both the stabilization of the quantity of stored water and the steady construction of the nest according to the given conditions. Perturbations of the system alter colony-level dynamics in a similar way as was observed in nature: water and pulp addition increase pulp arrivals and building rate; removal of pulp foragers decreases pulp input and construction rate, but not the water influx; removal of water foragers causes overcompensation of water input after a delay. After comparing the predictions of the model to natural data, assumptions found in the literature on organization of work and regulation of behavior are re-examined. A new, more parsimonious model of organization of work is proposed that may cover wide variety of cases where hormones and learning cannot be accounted for the regulation of behavior.     

Induction of glutathione-S-transferase in the Northern quahog Mercenaria mercenaria after exposure to the polychlorinated biphenyl (PCB) mixture Aroclor 1248

The glutathione-S-transferases (GSTs) from the Northern quahog (Mercenaria mercenaria) were examined after an injection of a polychlorinated biphenyl (PCB) mixture, Aroclor 1248, to a concentration of ~50 ppm. Enzymatic analysis indicated a fourfold increase in the GST activity of quahogs injected with PCBs compared with that of the control. An electrophoretic analysis of the GST from the PCB-exposed quahogs showed a 1.5-fold increase in the concentration over that of the control. Purification of the GST on a glutathione affinity column yielded a glutathione binding protein, in addition to the GSTs. However, the amount of the glutathione binding protein in the PCB-injected quahogs was found to decrease by ~50% in comparison to the glutathione binding protein in the control quahogs.     

Molecular phylogenetic exploration of bacterial diversity in a Bakreshwar (India) hot spring and culture of Shewanella-related thermophiles

The bacterial diversity of a hot spring in Bakreshwar, India, was investigated by a culture-independent approach. 16S ribosomal DNA clones derived from the sediment samples were found to be associated with gamma-Proteobacteria, cyanobacteria, and green nonsulfur and low-GC gram-positive bacteria. The first of the above phylotypes cobranches with Shewanella, a well-known iron reducer. This phylogenetic correlation has been exploited to develop culture conditions for thermophilic iron-reducing microorganisms.     

Inhibitory effect of galanin on dopamine induced increased oxytocin secretion in rat neurohypophyseal tissue cultures

The regulation of oxytocin (OT) release by galanin (GAL) at the neurohypophyseal (NH) nerve terminal is not adequately understood. The effect of GAL on the secretion of OT was studied in 13- to 14-day cultures of isolated rat NH tissue. By this time, the hormone content of the medium had become constant. The OT content of the supernatant medium was determined by RIA after a 1- or 2-h incubation. A significantly decreased content of OT was found following incubation with 10(-6)-10(-8) M doses of GAL. Dopamine (DA) and the DA-active drugs apomorphine (APM) and Pro-Lys-Gly (PLG) (10(-6) M in each medium) increased the OT synthesis of NH tissue cultures. This elevation of OT secretion could be blocked by the administration of GAL together with DA, APM or PLG. The DA-blocking effect of GAL was prevented by previous treatment with the GAL receptor antagonist galantid (M15). The results indicate that OT release from the NH is directly influenced by the GAL-ergic system. The GAL-ergic control of OT secretion from NH tissue in rats can occur at the level of the posterior pituitary.     

De novo translocation (2;18)(q21;q22) in a child with severe epilepsy, developmental delay and mild dysmorphism

De novo translocation (2;18)(q21;q22) in a patient with severe epilepsy developmental delay and mild dysmorphism: We report on a patient presenting with severe epilepsy, hypotonia, developmental delay, blepharophimosis, low-set ears, camptodactyly and tapering fingers, and cutaneous syndactyly of toes II and III of the right foot. The MRI showed some loss of volume of the white matter and delayed myelination, no other specific anomalies were present. Chromosome analysis revealed a translocation involving chromosomes 2 and 18, which was characterized further by FISH using band-specific probes. The possibility of a submicroscopic deletion is discussed and the patient is compared with patients reported in the literature with either 2q21 or 18q22 deletion.     

Molecular models in nickel carcinogenesis

Nickel compounds are known human carcinogens, but the exact molecular mechanisms of nickel carcinogenesis are not known. Due to their abundance, histones are likely targets for Ni(II) ions among nuclear macromolecules. This paper reviews our recent studies of peptide and protein models of Ni(II) binding to histones. The results allowed us to propose several mechanisms of Ni(II)-inflicted damage, including nucleobase oxidation and sequence-specific histone hydrolysis. Quantitative estimations of Ni(II) speciation, based on these studies, support the likelihood of Ni(II) binding to histones in vivo, and the protective role of high levels of glutathione. These calculations indicate the importance of histidine in the intracellular Ni(II) speciation.