Numerical exploration of the influence of neural noise on the psychometric function at low stimulation intensity levels

The relationship between stimulus intensity and the probability of detecting the presence of the stimulus is described by the psychometrical function. The probabilistic nature of this relationship is based on the stochastic behaviour of sensory neural channels and sensory networks involved in perceptual processing (Kiang 1968). This study tries to establish a continuum of variability across different levels of integration in the central nervous system. Once the opening and closing times of ionic channels was simulated, a threshold to the collective behaviour of voltage-gated ionic channels was imposed in order to generate the spike train of a single neuron. Afterwards, the trains of spikes of different neurons were added up, simulating the activity of a sensory nerve. By adding the activity due to the stimulus to the spontaneous neural behaviour, the psychometric function was simulated using a thresholding approach. The results can replicate the stochastic resonance phenomenon, but also open up the possibility that attentional phenomena can be mediated not only by increasing neural activity (bursting or oscillatory), but also by increasing noise at the neural level.     

Assessment of the mechanical activity of cardiac isomyosins V1 and V3 by the in vitro motility assay with regulated thin filament

The dependences of thin filament sliding velocity on the calcium concentration in solution (pCa 5 to 8) for rabbit cardiac myosin isoforms V1 and V3 were determined in a set of experiments using an in vitro motility assay with a reconstructed thin filament. The constructed pCa-versus-velocity curves had a sigmoid shape. It was demonstrated that the sliding velocity of regulated thin filament at the saturating calcium concentration (pCa 5) did not differ from the actin sliding velocity for each isoform. The determined values of Hill’s cooperativity coefficient for isomyosins V1 and V3 were 1.04 and 0.75, respectively. It was demonstrated that isomyosin V3 was more sensitive to calcium as compared with isomyosin V1. Using the same assay, the dependence of thin filament sliding velocity on the concentration of the actin-binding protein α-actinin (analog of a force-velocity dependence) was determined at the saturating calcium concentration for each myosin isoform (V1 and V3). The results suggest that the calcium regulation of V1 and V3 contractile activity follows different mechanisms.     

Characteristics of GABA Release Induced by Free Radicals in Mouse Hippocampal Slices

The release of the inhibitory neurotransmitter GABA is generally enhanced under potentially cell-damaging conditions. The properties and regulation of preloaded [³H]GABA release from mouse hippocampal slices were now studied in free radical-containing medium in a superfusion system. Free radical production was induced by 0.01% of H₂O₂ in the medium. H₂O₂ markedly potentiated GABA release, which was further enhanced about 1.5-fold by K⁺ stimulation (50 mM). In Ca²⁺-free media this stimulation was not altered, indicating that the release was mostly Ca²⁺-independent. Moreover, omission of Na⁺ increased the release, suggesting that it is mediated by Na⁺-dependent transporters operating outwards, a conception confirmed by the enhancement with GABA homoexchange. Inhibition of the release with the ion channel inhibitors diisothiocyanostilbene-2,2′-disulphonate and 4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonate indicates that Cl⁻ channels also participate in the process. This release was not modified by the adenosine receptor (A₁ and A_2a) agonists and ionotropic glutamate receptor agonists kainate, N-methy-d-aspartate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, whereas the agonists of metabotropic glutamate receptors of group I [(S)-3,5-dihydroxyphenylglycine] and of group II [(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate] enhanced it by receptor-mediated mechanisms, the effects being abolished by their respective antagonists. The group III agonist l(+)-2-amino-4-phosphonobutyrate reduced the evoked GABA release, but this was not affected by the antagonist. Furthermore, the release was reduced by activation of protein kinase C by 4β-phorbol 12-myristate 13-acetate and by inhibition of tyrosine kinase by genistein and of phoshoplipase by quinacrine. On the other hand, increasing cGMP levels with the phosphodiesterase inhibitor zaprinast, selective for PDE5, 6 and 9, and NO production with the NO-generating compounds hydroxylamine, sodium nitroprusside and S-nitroso-N-penicillamine enhanced the release. The regulation of GABA release induced by free radical production proved thus to be rather complex. Under potentially cell-damaging conditions, the potentiation of GABA release may be a mechanism to counteract hyperactivity and reduce the effects of excitatory amino acid release. On the other hand, reduction of GABA release could be harmful and contribute to excitotoxic damage and neuronal degeneration.     

A Basis for Spatial and Social Patterns in Ant Species: Dynamics and Mechanisms of Aggregation

Aggregation is usually studied in functional terms, forgetting mechanisms. In this paper, experimental results on the ant Lasius niger, complemented by a model, allow us to understand the mechanisms responsible for aggregation and to study the influence of the population density on this phenomenon. The results show (1) a high level of aggregation and the emergence of a large cluster; (2) that aggregation results from an amplification mechanism—the greater the number of ants inside a cluster, the greater the time spent by one ant in this cluster; and (3) that population density has only a weak influence on the aggregation process. This method of analysis and these results can certainly be extended not only in social insects but also in other species, like subsocial arthropods.     

Comparison of the Mutation Spectrum of Hypervariable Segment 1 for Phylogeographical Groups of Human Mitochondrial DNA

The nucleotide sequence variation of hypervariable segment 1 (HVS1) was analyzed for mtDNAs of 88 phylogeographical clusters characteristic of African, West Eurasian, or East Eurasian populations. A significant difference in the distribution of mutations was revealed for the mitochondrial gene pools of the regional human populations. The HVS1 positions were identified whose instability is explained by strand displacement during mtDNA replication. Strand displacement was assumed to be a major mechanism of context-dependent mutagenesis associated with the regional differentiation of human populations.     

Host plant resistance against broomrapes (Orobanche spp.): defence reactions and mechanisms of resistance

Over 4000 species of angiosperms are able to directly invade and parasitise other plants, but only very few are weedy and parasitise cultivated plants. Together with the witchweeds (Striga spp.) and dodders (Cuscuta spp.), the broomrapes (Orobanche spp.) affect important crops causing complete yield loses with severe infestations. Genetic resistance to parasitisation remains as one of the most desirable components in an integrated control strategy. However, breeding for resistance is a difficult task and many aspects of the host/parasite interaction remain unknown. In the present work, we review the cytological and cytochemical studies investigating the mechanisms of resistance involved in the process leading to an incompatible host–parasite interaction. We have attempted to identify the main gaps and problems related to such studies with parasitic plants and present an in‐depth review of histochemical techniques used to assess mechanisms of resistance against these parasitic plants. Furthermore, we discuss future research directions and novel techniques and finally, how such techniques can be applied and incorporated within a breeding programme.     

An anaerobic bacterial MsrB model reveals catalytic mechanisms, advantages, and disadvantages provided by selenocysteine and cysteine in reduction of methionine-R-sulfoxide

We verified and generalized the catalytic features that selenocysteine (Sec) and cysteine (Cys) contribute to the reduction of methionine-R-sulfoxide using an anaerobic bacterial MsrB from Clostridium sp. OhILA as a model protein. The Sec-containing Clostridium MsrB form exhibited 100-fold higher activity than its Cys-containing form, revealing that Sec provided the catalytic advantage of higher activity. However, a resolving Cys was required for the thioredoxin (Trx)-dependent recycling process of the Sec-containing form. Thus, Trx could reduce the selenenylsulfide bond, but its Trx-dependent recycling process was much less efficient compared to that for the disulfide bond in the Cys-containing form, demonstrating an obvious catalytic disadvantage. These data agreed well with our previous data on mammalian MsrBs, and therefore suggested that the catalytic mechanisms, as well as the catalytic advantages and disadvantages provided by the Sec and Cys residues, are most likely conserved from anaerobic bacteria to mammals. Taken together, we propose that the use of Sec in MsrB may depend on a balance between the catalytic advantage of higher activity and the disadvantage of a less efficient regeneration process provided by this residue.     

Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase

Intravenous enzyme replacement therapy (ERT) with purified glucocerebrosidase (GLA) leads to significant improvement of the clinical manifestations in patients with Type 1 Gaucher disease. However, the high doses required, slow response and inability to recover most of the infused enzyme in the target tissues may be attributed to losses occurring during transit en route to the lysosome. Preincubation of GLA with isofagomine (IFG), a slow-binding inhibitor, significantly increased stability of the enzyme to heat, neutral pH and denaturing agents in vitro. Preincubation of GLA with isofagomine prior to uptake by cultured cells results in increased intracellular enzyme activity accompanied by an increase in enzyme protein suggesting that reduced denaturation of GLA in the presence of isofagomine leads to a decrease in the degradation of the enzyme after internalization. Preincubation of GLA with slow-binding inhibitors before infusion may improve the effectiveness of ERT for Gaucher disease.