Evaluation of binaural interaction according to the characteristics of short latency acoustic evoked potentials in guinea pigs

Binaural interactions was evaluated in guinea pigs by plotting the difference between the algebraic sum of brainstem evoked potentials recorded during monaural stimulation of the right and left ears and those produced by binaural stimuli. This plot was distinguished by three peaks (N₁, P₁, and N₂) in the region of IV–IV wave latencies (short-latency acoustic evoked potentials) in the absence of masking noise, but using masking noise (signal-noise ratio: +20-0 dB), plots showed additional peaks No and Po in the region of wave III–III latencies. The amplitude of P₁N₂ in relation to that of wave IV of the summated potentials recording monaural stimulation of the right and left ear remains constant with an increase in the sound pressure level from 47 to 107 dB. This relationship grows with a decline in the signal-noise ratio when masking is used, while the P₁N₂ amplitude declines. It is postulated that binaural interaction pattern does not change when the clicking sound increases in intensity and that distinctive aspects of neurophysiological mechanisms underlying binaural interaction emerge during masking with a signal-noise ratio of +20-0 dB.Institute of Otolaryngology, Ministry of Public Health of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 5, pp. 579–586, September–October, 1987.     

Bacterial interactions with the autophagic pathway

Bacteria have evolved a variety of mechanisms to invade eukaryotic cells and survive intracellularly. Once inside, bacterial pathogens often modulate their phagosome to establish an intracellular niche for survival and replication. A subset of intracellular pathogens, including Brucella abortus, Legionella pneumophila and Porphyromonas gingivalis, are diverted from the endosomal pathway to the auto-phagic pathway. Once within the autophagosome, each in some way presumably modifies this compartment to establish an environment necessary for its survival. Transit into autophagosomes represents an avenue by which to escape host defences. In this review, we examine the biochemical and morphological evidence for the survival of some bacterial pathogens by replicating within an autophagosome-like compartment.     

Docking interactions in the c-Jun N-terminal kinase pathway

The c-Jun N-terminal kinase (JNK) signaling pathway is a major mediator of stress responses in cells. Similar to other mitogen-activated protein kinases (MAPKs), JNK activity is controlled by a cascade of protein kinases and by protein phosphatases, including dual-specificity MAPK phosphatases. Components of the JNK pathway associate with scaffold proteins that modulate their activities and cellular localization. The JNK-interacting protein-1 (JIP-1) scaffold protein specifically binds JNK, MAPK kinase 7 (MKK7), and members of the mixed lineage kinase (MLK) family, and regulates JNK activation in neurons. In this study we demonstrate that distinct regions within the N termini of MKK7 and the MLK family member dual leucine zipper kinase (DLK) mediate their binding to JIP-1. We have also identified amino acids in JNK required for: (a) binding to JIP-1 and for JIP-1-mediated JNK activation, (b) docking to MAPK kinase 4 (MKK4) and efficient phosphorylation by MKK4, and (c) docking to its substrate c-Jun and efficient c-Jun phosphorylation. None of the amino acids identified were essential for JNK docking to MKK7 or the dual-specificity phosphatase MAPK phosphatase 7 (MKP7). These findings uncover molecular determinants of JIP-1 scaffold complex assembly and demonstrate that there are overlapping, but also distinct, binding determinants within JNK that mediate interactions with scaffold proteins, activators, phosphatases, and substrates.     

Development of brainstem auditory pathway in mallard duck embryos and hatchlings

Summary The development of the brainstem auditory evoked potential (BAEP) was studied in mallard duck (Anas platyrhynchos) embryos and hatchlings from 5–6 days before hatching through two days after hatching in response to tone pips of different frequencies. BAEPs showed a different time of onset and a different rate of development for low, middle, and high frequencies. Although auditory sensitivity in the mid-frequency range (1.0, 1.5, 2.0, and 3.0 kHz) appeared 1–2 days later than in the low-frequency range, development of the BAEPs in the mid-frequency range was almost complete by hatching. In contrast, the development of auditory sensitivity in the low- and high-frequency ranges continued to develop after hatching. Accelerated development of BAEPs to middle frequencies during the embryonic period and to high frequencies after hatching was correlated with the ducklings' exposure to their own mid-frequency and high-frequency vocalizations before and after hatching, respectively.Abbreviations BAEP brainstem auditory evoked potential - CM cochlear microphonic - CT contact-contentment call - DT distress call - EP evoked potential     

Water-mediated ionic interactions in protein structures

It is well known that water molecules play an indispensable role in the structure and function of biological macromolecules. The water-mediated ionic interactions between the charged residues provide stability and plasticity and in turn address the function of the protein structures. Thus, this study specifically addresses the number of possible water-mediated ionic interactions, their occurrence, distribution and nature found in 90% non-redundant protein chains. Further, it provides a statistical report of different charged residue pairs that are mediated by surface or buried water molecules to form the interactions. Also, it discusses its contributions in stabilizing various secondary structural elements of the protein. Thus, the present study shows the ubiquitous nature of the interactions that imparts plasticity and flexibility to a protein molecule.     

Dust ion acoustic solitary structures in the presence of isothermal positrons

The Sagdeev potential technique has been employed to study the dust ion acoustic solitary waves and double layers in an unmagnetized collisionless dusty plasma consisting of negatively charged static dust grains, adiabatic warm ions, isothermally distributed electrons, and positrons. A computational scheme has been developed to draw the qualitatively different compositional parameter spaces or existence domains showing the nature of existence of different solitary structures with respect to any parameter of the present plasma system. The present system supports both positive and negative potential double layers. The negative potential double layer always restricts the occurrence of negative potential solitary waves, i.e., any sequence of negative potential solitary waves having monotonically increasing amplitude converges to a negative potential double layer. However, there exists a parameter regime for which the positive potential double layer is unable to restrict the occurrence of positive potential solitary waves. As a result, in this region of the parameter space, there exist solitary waves after the formation of positive potential double layer, i.e., positive potential supersolitons have been observed.     

Mapping of cholinoceptive brainstem structures responsible for the generation of paradoxical sleep in the cat

In order to determine the cholinoceptive brainstem structures critical for PS generation, we investigated the effect on PS induction of the injection of a small dose and volume (0.4 microgram/0.2 microliter) of the cholinergic agonist carbachol in the following caudal brainstem structures: 1) the caudal mesencephalic reticular formation, especially the nucleus pedunculopontinus pars compacta or X area; 2) the mediodorsal pontine tegmentum, in particular the nuclei locus coeruleus (LC), locus coeruleus alpha (LC alpha), peri-locus coeruleus alpha (peri-LC alpha) and laterodorsalis tegmenti (Ldt); 3) the pontine; and 4) bulbar gigantocellular (FTG) and magnocellular tegmental fields (FTM). We found that the only brainstem area from which a high amount of PS was induced by carbachol applications with short latencies, less than 5 minutes, is the mediodorsal pontine tegumentum, namely the LC alpha and peri-LC alpha, where ChAT-and TH- immunoreactive neurons are intermingled. Injections in an area immediately ventral to the peri-LC alpha induced physiological states resembling PS but lacking certain electrophysiological (PS-like) and behavioral components of PS (dissociated states I and II). The weak PS induction following carbachol administration in the anteromedial part of the FTG was due to the spread of the drug toward the efficient site since the latencies to PS onset were in the range of 20 to 60 minutes. No effects on PS generation were obtained after carbachol microinjections in the LC and the laterocaudal part of the FTG, while carbachol injections in the X area or in the bulbar FTG or FTM resulted in the increase of waking and the decrease of PS. In addition to these effects on PS induction, we also found that carbachol induced: 1) stereotyped PGO-like bursts when injected in the ventral part of the FTG and the rostral part of the FTM, 2) postural atonia with very short latencies, less than two minutes, when injected in the LC alpha and peri-LC alpha; and 3) hippocampal theta waves of 3-5 Hz persisting during light slow wave sleep (S1) when injected in and around the LC alpha and peri-LC alpha and in some points of the mediocaudal part of the FTG. These results support the hypothesis that PS is generated by highly localized neuronal populations and suggest that the mediodorsal pontine tegmentum (namely the nuclei LC alpha and peri-LC alpha) may represent a cholinoceptive PS generator.     

Bacterial interactions with the eukaryotic secretory pathway

Pathogenic bacteria exploit a wide variety of host cellular processes to adhere to, invade, replicate within and damage host cells. One such process is the eukaryotic secretory pathway, in which proteins and lipids are modified and transported from the endoplasmic reticulum through the Golgi network to the plasma membrane and other cellular destinations. Certain bacteria secrete toxins that utilise this transport pathway to reach their cellular targets. Some intracellular pathogens, including Legionella, Brucella and Chlamydia, engage other steps of the pathway to establish intracellular replicative organelles. Recent work has implicated specific virulence proteins of enterohaemorrhagic Escherichia coli and Salmonella enterica in secretory pathway interactions.     

Neuro-immune interactions via the cholinergic anti-inflammatory pathway

The overproduction of TNF and other cytokines is associated with the pathophysiology of numerous diseases. Controlling cytokine synthesis and release is critical for preventing unrestrained inflammation and maintaining health. Recent studies identified an efferent vagus nerve-based mechanism termed "the cholinergic anti-inflammatory pathway" that controls cytokine production and inflammation. Here we review current advances related to the role of this pathway in neuro-immune interactions that prevent excessive inflammation. Experimental evidence indicates that vagus nerve cholinergic anti-inflammatory signaling requires alpha7 nicotinic acetylcholine receptors expressed on non-neuronal cytokine-producing cells. Alpha7 nicotinic acetylcholine receptor agonists inhibit cytokine release and protect animals in a variety of experimental lethal inflammatory models. Knowledge related to the cholinergic anti-inflammatory pathway can be exploited in therapeutic approaches directed towards counteracting abnormal chronic and hyper-activated inflammatory responses.     

Functional changes in brainstem auditory structures in humans suffering from the Chernobyl’ catastrophe

We analyzed the temporal characteristics of short-latency auditory evoked potentials (SL AEP) in people involved in the cleanup work after the Chemobyl’ catastrophe (hereafter, cleanup workers), who now are living within the “clean” territories or remain within the radionuclide-contaminated area (groups 2 and 3, respectively), and in persons who were not involved in the cleanup works but are permanently living within the contaminated zone (group 4). The latencies of the SL AEP were peaks (peak latencies, PL) in all these groups regularly exceeded corresponding values in the control group 1. The increments were mild (several percent) but significant for the waves II–V. The most substantial PL increments were characteristic for group 3. Analysis of the interpeak intervals showed that an increase in the I–III interval provided the greatest contribution to modification of the SL AEP, temporal parameters. The mechanisms of influence of the Chernobyl’ catastrophe-related factors on the brainstem auditory structures are discussed. The data allow us to conclude that functional modifications in the above structures contribute to the hearing change for the worse observed in the people suffering from the Chernobyl’ catastrophe; a prolonged stay within the contaminated territories represents a considerable factor aggravating these changes.     

Ligand receptor interactions in the Wnt signaling pathway in Drosophila

Secreted Wnt proteins have numerous signaling functions during development, mediated by Frizzled molecules that act as Wnt receptors on the cell surface. In the genome of Drosophila, seven Wnt genes (including wingless; wg), and five frizzled genes have been identified. Relatively little is known about signaling and binding specificities of different Wnt and Frizzled proteins. We have developed an assay to determine the strength of binding between membrane-tethered Wnts and ligand binding domains of the Frizzled receptors. We found a wide spectrum of binding affinities, reflecting known genetic interactions. Most Wnt proteins can bind to multiple Frizzleds and vice versa, suggesting redundancy in vivo. In an extension of these experiments, we tested whether two different subdomains of the Wg protein would by themselves bind to Frizzled and generate a biological response. Whereas these two separate domains are secreted from cells, suggesting that they form independently folded parts of the protein, they were only able to evoke a response when co-transfected, indicating that both are required for function. In addition to the Frizzleds, members of the LRP family (represented by the arrow gene in Drosophila) are also necessary for Wnt signal transduction and have been postulated to act as co-receptors. We have therefore examined whether a soluble form of the Arrow molecule can bind to Wingless and Frizzled, but no interactions were detected.     

Features of the aggressive behavior of victorious mice in inter-male interactions

Latency of the first attack, number of attacks and total attacking time in aggressive male C57BL/6J strain mice were studied during agonistic interactions with submissive mice which had a great defeat experience. Then, aggressive mice were placed together in order to find out which will be the winner in each pair. It has been shown that males with a shorter latency of the first attack and greater total attacking time gained the victory.