Influence of the solvent on the conformational-dependent properties of random-coil polypeptides. I. The mean-square of the end-to-end distance and of the dipole moment

Conformational energies for the N-acetyl-N'-methylamides of the 20 natural amino acids were calculated, including the solvent effects, as functions of the angles phi and psi for rotation of the main chain and for six positions chi 1 of the C alpha-C beta bond in the side chain (fixed values for chi 2, chi 3, ...). The computed energies were used to evaluate the mean-square end-to-end distance and mean-square dipole moment of homopolypeptides of the 20 natural amino acids. Ten proteins and three enzymes of current interest were also studied. Slight differences in both properties are found on taking the effects of solvent into consideration. Comparison with other computational and experimental results is made.     

Effect of Inflammatory Stimuli on the Silver Staining Pattern of the Rat Carotid Endothelium

Silver nitrate stains the intercellular junctions of the endothelium and other cytoplasmic or membrane components. Two protocols are described for the silver staining of rat carotid endothelium that exclude the use of pressurized fixatives and simplify the technique previously described for rat aorta. The entire surface of the carotid endothelium was examined and several parameters (stigmata, granularity, clustering of anionic sites, transversal lines, weakening of silver lines and leukocyte adhesion) were evaluated. We studied the pattern of silver staining in two situations: (1) endothelial activation and (2) neurogenic inflammation. Endothelial activation was produced by the intravenous administration of a proinflammatory albumin or polyinosinic acid. Both products cause a marked increase in leukocyte adhesion concomitant with a decrease in argyrophilia and a weakness or loss of silver lines. Neurogenic inflammation, which is mediated by substances released from sensory nerves, was induced by the intravenous administration of substance P or capsaicin. Both stimuli produced an increase in argyrophilia and weakness or loss of silver lines. Substance P caused a clustering of anionic sites, whereas this phenomenon was more discrete with capsaicin. Nearly 80% of all examined rats (controls and inflammatory stimuli treated) showed endothelial membrane disruptions formed by clusters of cells often in the shape of streaks aligned with the long axis of the vessel. The detection of these discontinuities is important, as loss of endothelial integrity is central in the initiation of pathological events.     

Ruthenium red inhibits mitochondrial Na+ and K+ uniports induced by magnesium removal.

Removal of bound magnesium from the outer surface of the inner mitochondrial membrane opens up a Na+ and Li+ selective electrophoretic uniport pathway whereas simultaneous depletion of intramitochondrial magnesium induces an electrogenic K+ flux as well. In order to clarify the nature of these cation movements we tested the effect of ruthenium red, a potent and specific inhibitor of the mitochondrial Ca2+ uniporter on different Na+ and K+ uniport-associated phenomena. Ruthenium red efficiently inhibited mitochondrial swelling and depolarization induced by either EDTA in a NaCl-based medium (Na+ uniport) or by EDTA plus A23187 in a KCl-based medium (K+ uniport). For both cation uniports half-maximal inhibition was attained at a ruthenium red concentration as low as 40 nM. Complete inhibition was found above 200 nM. Neither the Na+/H+ nor the K+/H+ exchange was affected by ruthenium red. In light of these observations the possibility is raised that the electrogenic Na+ and K+ fluxes provoked by magnesium reduction or depletion may be mediated through the Ca2+ uniporter. It is suggested that intactness of the mitochondrial magnesium pools is necessary for maintaining the Ca2+ selectivity of the Ca2+ uniporter, and alterations of the membrane-associated magnesium content would make this transport route available also for monovalent cations.     

How the Visual Cortex Handles Stimulus Noise: Insights from Amblyopia

Adding noise to a visual image makes object recognition more effortful and has a widespread effect on human electrophysiological responses. However, visual cortical processes directly involved in handling the stimulus noise have yet to be identified and dissociated from the modulation of the neural responses due to the deteriorated structural information and increased stimulus uncertainty in the case of noisy images. Here we show that the impairment of face gender categorization performance in the case of noisy images in amblyopic patients correlates with amblyopic deficits measured in the noise-induced modulation of the P1/P2 components of single-trial event-related potentials (ERP). On the other hand, the N170 ERP component is similarly affected by the presence of noise in the two eyes and its modulation does not predict the behavioral deficit. These results have revealed that the efficient processing of noisy images depends on the engagement of additional processing resources both at the early, feature-specific as well as later, object-level stages of visual cortical processing reflected in the P1 and P2 ERP components, respectively. Our findings also suggest that noise-induced modulation of the N170 component might reflect diminished face-selective neuronal responses to face images with deteriorated structural information.     

Gabaergic Pharmacological Activity of Propofol Related Compounds as Possible Enhancers of General Anesthetics and Interaction with Membranes

Phenol compounds, such as propofol and thymol, have been shown to act on the GABA_A receptor through interaction with specific sites of this receptor. In addition, considering the high lipophilicity of phenols, it is possible that their pharmacological activity may also be the result of the interaction of phenol molecules with the surrounding lipid molecules, modulating the supramolecular organization of the receptor environment. Thus, in the present study, we study the pharmacological activity of some propofol- and thymol-related phenols on the native GABA_A receptor using primary cultures of cortical neurons and investigate the effects of these compounds on the micro viscosity of artificial membranes by means of fluorescence anisotropy. The phenol compounds analyzed in this article are carvacrol, chlorothymol, and eugenol. All compounds were able to enhance the binding of [³H]flunitrazepam with EC₅₀ values in the micromolar range and to increase the GABA-evoked Cl^? influx in a concentration-dependent manner, both effects being inhibited by the competitive GABA_A antagonist bicuculline. These results strongly suggest that the phenols studied are positive allosteric modulators of this receptor. Chlorothymol showed a bell-type effect, reducing its positive effect at concentrations >100 μM. The concentrations necessary to induce positive allosteric modulation of GABA_A receptor were not cytotoxic. Although all compounds were able to decrease the micro viscosity of artificial membranes, chlorothymol displayed a larger effect which could explain its effects on [³H]flunitrazepam binding and on cell viability at high concentrations. Finally, it is suggested that these compounds may exert depressant activity on the central nervous system and potentiate the effects of general anesthetics.     

Adrenergic modulation of immune cells: an update

Sympathoadrenergic pathways are crucial to the communication between the nervous system and the immune system. The present review addresses emerging issues in the adrenergic modulation of immune cells, including: the specific pattern of adrenoceptor expression on immune cells and their role and changes upon cell differentiation and activation; the production and utilization of noradrenaline and adrenaline by immune cells themselves; the dysregulation of adrenergic immune mechanisms in disease and their potential as novel therapeutic targets. A wide array of sympathoadrenergic therapeutics is currently used for non-immune indications, and could represent an attractive source of non-conventional immunomodulating agents.     

Interspecific Introgression in Cetaceans: DNA Markers Reveal Post-F1 Status of a Pilot Whale

Visual species identification of cetacean strandings is difficult, especially when dead specimens are degraded and/or species are morphologically similar. The two recognised pilot whale species (Globicephala melas and Globicephala macrorhynchus) are sympatric in the North Atlantic Ocean. These species are very similar in external appearance and their morphometric characteristics partially overlap; thus visual identification is not always reliable. Genetic species identification ensures correct identification of specimens. Here we have employed one mitochondrial (D-Loop region) and eight nuclear loci (microsatellites) as genetic markers to identify six stranded pilot whales found in Galicia (Northwest Spain), one of them of ambiguous phenotype. DNA analyses yielded positive amplification of all loci and enabled species identification. Nuclear microsatellite DNA genotypes revealed mixed ancestry for one individual, identified as a post-F1 interspecific hybrid employing two different Bayesian methods. From the mitochondrial sequence the maternal species was Globicephala melas. This is the first hybrid documented between Globicephala melas and G. macrorhynchus, and the first post-F1 hybrid genetically identified between cetaceans, revealing interspecific genetic introgression in marine mammals. We propose to add nuclear loci to genetic databases for cetacean species identification in order to detect hybrid individuals.     

Stone Throwing as a Sexual Display in Wild Female Bearded Capuchin Monkeys,Sapajus libidinosus

Capuchin monkeys (Sapajus spp.) in captive settings frequently manipulate and throw objects. In the wild, they may push or drop stones and sticks toward targets during inter- or intraspecific threat displays. In addition, female capuchin monkeys exhibit a broad repertoire of behaviors during their proceptive period, including facial expressions, vocalizations, stereotyped body postures, and touch-and-run behavior. This study reports stone throwing as a newly-described communicative behavior during the proceptive display of females in a group of bearded capuchin monkeys (S. libidinosus) in Serra da Capivara National Park, Brazil. During a two-year study, three females from one group were seen throwing stones at males during their proceptive phase. After this period, three other females in the same group exhibited the same behavior. Although it may be possible that this pattern is the result of several independent innovations by each female, the apparent absence of this behavior in other groups leads us to suggest that we have documented the diffusion of a new behavioral trait or tradition within this capuchin social group.