1,721,081 research outputs found
Potentiation and inhibition of neuronal α4β4 nicotinic acetylcholine receptors by choline
No full textNeurotoxicological effects and the mode of action of pyrethroid insecticides
No full textNeuroexcitatory symptoms of acute poisoning of vertebrates
by pyrethroids are related to the ability of these insecticides to
modify electrical activity in various parts of the nervous system.
Repetitive nerve activity, particularly in the sensory nervous
system, membrane depolarization, and enhanced neurotransmitter
release, eventually followed by block of excitation, result
from a prolongation of the sodium current during membrane
excitation. This effect is caused by a stereoselective and
structure-related interaction with voltage-dependent sodium
channels, the primary target site of the pyrethroids.
Near-lethal doses of pyrethroids cause sparse axonal damage
that is reversed in surviving animals. After prolonged exposure
to lower doses of pyrethroids axonal damage is not observed.
Occupational exposure to pyrethroids frequently leads to
paresthesia and respiratory irritation, which are probably due
to repetitive firing of sensory nerve endings. Massive exposure
may lead to severe human poisoning symptoms, which are
generally treated well by symptomatic and supportive measures
Incomplete lineage sorting rather than hybridization explains the inconsistent phylogeny of the wisent
No full textThe wisent or European bison is the largest European herbivore and is completely cross-fertile with its American relative. However, mtDNA genome of wisent is similar to that of cattle, which suggests that wisent emerged as a hybrid of bison and an extinct cattle-like species. Here, we analyzed nuclear whole-genome sequences of the bovine species, and found only a minor and recent gene flow between wisent and cattle. Furthermore, we identified an appreciable heterogeneity of the nuclear gene tree topologies of the bovine species. The relative frequencies of various topologies, including the mtDNA topology, were consistent with frequencies of incomplete lineage sorting (ILS) as estimated by tree coalescence analysis. This indicates that ILS has occurred and may well account for the anomalous wisent mtDNA phylogeny as the outcome of a rare event. We propose that ILS is a possible explanation of phylogenomic anomalies among closely related species
Antigenicity of the peplomer protein of infectious bronchitis virus
No full textTo study the antigenic structure of the peplomer protein of the avian coronavirus infectious bronchitis virus, fragments from the peplomer gene were generated by restriction-enzyme cleavage or by limited DNase digestion and inserted in the Escherichia coli expression plasrnid pEX (Stanley and Luzio, 1984). The antigenicity of the expression products was tested using a number of polyclonal antisera and monoclonal antibodies. The polyclonal antisera recognized different sets of epitopes in the 1162-residue sequence. The N-terminal region of one of the two subunits, S2, was recognized by all polyclonal sera and by two monoclonal antibodies. This clearly immunodominant region contains at least two adjacent or overlapping epitopes, one of which has been localized within 18 residues. The epitopes found as antigenic pEX expression products do not coincide with the regions in the S1 subunit that have been found to contain hypervariable sequences. We suggest that these regions constitute conformation dependent neutralization epitopes that cannot be detected in the pEX system. The relevance of our finclings for vaccine development is discussed
Ciguatoxin is a novel of type of Na+ channel toxin
No full textPurified ciguatoxin at 0.1 to 10 ng/ml inhibits the net accumulation of neurotransmitters (y-aminobutyric acid and dopamine) by brain synaptosomes. This action is due to a stimulation of neurotransmitter release. The half-maximum effect of the toxinis observed at 0.62 ng/ml. The effect of ciguatoxin is completely inhibited by tetrodotoxin = 4 nM). Electrophysiological studies on neuroblastoma cells indicate that ciguatoxin induces a membrane depolarization which is prevented by tetrodotoxin and which is due to an action that increases Na+ permeability. Under appropriate conditions ciguatoxicnr eates spontaneous oscillations in the membrane polarization level and repeated action potentials. Ciguatoxin stimulates 22Na+ entry through the voltage-dependent Na+ channels of neuroblastoma cells and rat skeletal myoblasts when it is used in synergy with veratridine, batrachotoxin, pyrethroids, sea anemone, or scorpion toxins. The half-maximum effect of ciguatoxin on 22Na+ flux in the presence of veratridine occurs at a concentration of 0.5 ng/ml. Stimulation of 22Na+ flux by ciguatoxin is abolished by tetrodotoxin. These results taken together indicate that ciguatoxin belongs to a new class of toxins acting on Na+ channels
Selective inhibition of γ-aminobutyric acid type A receptors in human IMR-32 cells by low concentrations of toluene
No full textEffects of the neurotoxic organic solvent toluene on human neuronal nicotinic acetylcholine (nACh) and gaminobutyric acid type A (GABAA) neurotransmitter receptors were investigated in whole-cell voltage-clamped IMR- 32 neuroblastoma cells. Ion currents evoked by near maximum effective concentrations of 1 mM acetylcholine (ACh) and 1 mM g-aminobutyric acid (GABA) are inhibited by toluene in a concentration-dependent way. Concentration/ effect curves of toluene yield IC50 values of 2769/26 and 399/6 mM and slope factors of 1.49/0.2 and 0.89/0.1 for inhibition of the ACh- and GABA-induced ion currents, respectively. The results demonstrate the selective inhibition of human GABAA receptors by toluene at concentrations comparable with brain concentrations associated with occupational exposure
Analysis and simulation of a neutralizing epitope of transmissible gastroenteritis virus
No full textThe amino acid sequences recognized by monoclonal antibodies (MAbs) specific for the antigenic site IV of the spike protein S of transmissible gastroenteritis virus were analyzed by PEPSCAN. All MAbs of group IV recognized peptides from the S region consisting of residues 378 to 390. In addition, the neutralizing MAbs (subgroup IV-A) also bound to peptides from the region consisting of residues 1173 to 1184 and to several other peptides with a related amino acid composition. The contribution of the individual residues of both sequences to the binding of a MAb was determined by varying the length of the peptide and by a consecutive deletion or replacement of parental residues by the 19 other amino acids. The sequence consisting of residues 326 to 558, tested as part of a cro-β-galactosidase hybrid protein, was antigenic, but the sequence consisting of residues 1150 to 1239 was not. Furthermore, antibodies raised in rabbits against the peptide SDSSFFSYGEIPFGN (residues 377 to 391), but not those raised against the peptide VRASRQLAKDKVNEC (residues 1171 to 1185), recognized the virus and had neutralizing activity. We infer that the epitope of the neutralizing MAbs is composite and consists of the linear sequence SFFSYGEI (residues 380 to 387) with contributions of A, D, K, N, Q, or V residues from other parts of the S molecule. The complex epitope was simulated by sythesizing peptides in which the sequences consisting of residues 380 to 387 and 1176 to 1184 were combined. MAbs of subgroup IV-A recognized the combination peptides two to six times better than the individual sequences. These results may offer prospects for the development of an experimental vaccine
Phylogeny of antigenic variants of avian coronavirus IBV
No full textThe sequences of the peplomeric S1 protein of four serologically distinct strains of the infectious bronchitis virus (IBV), an avian coronavirus, have been determined. The S1 protein is thought to contain the serotype-specific neutralization epitopes and to be the main target of antigenic variation. An alignment with sequences of three strains published previously showed that from the 545 amino acid residues only 243 have been conserved. Clustering of substitutions suggests that most serotype determinants are located within the first 300 amino acid residues of S1. A phylogenetic tree of the S1 sequences showed very variable rates of divergence. Differences in topology with a tree based on RNAse-T1 fingerprint data indicate that some of the IBV strains have arisen by genetic recombination
Perceived immune functioning and sleep
No full textIntroduction: The interaction between sleep and biomarkers of immune functioning (e.g., altered cytokine profiles) has been shown previously. The aim of this study was to investigate the relationship between perceived immune functioning and sleep in healthy young adults. Methods: Students of different Dutch universities participated in an online survey. Subscales of the SLEEP-50 questionnaire were completed to assess narcolepsy, insomnia, and circadian rhythm disorder (CRD). Total Sleep Time (TST), sleep quality, and number of nightly awakenings were assessed as well. Perceived immune functioning was assessed with the Immune function questionnaire (IFQ), and rated on a scale ranging from 0 (very poor) to 10 (excellent). Associations between sleep outcomes were related to perceived immune functioning using nonparametric Spearman correlations. Results: A total of 2489 healthy students (16.8% men) completed the survey. Their mean (SD) age was 21.2 (2.1) years old. Perceived immune functioning, as assessed with the IFQ, correlated significantly with scores of insomnia (r = 0.282, p = 0.000), narcolepsy (r = 0.229, p = 0.000), and CRD (r = 0.166, p = 0.000). In line, perceived immune functioning assessed with the 1-item rating also correlated significantly with scores of insomnia (r = -0.193, p = 0.000), narcolepsy (r = -0.135, p = 0.000), and CRD (r = -0.136, p = 0.000). TST did not correlate significantly with perceived immune functioning. The number of nightly awakenings correlated significantly with both the IFQ score (r = 0.185, p = 0.000), and the 1-item perceived immune functioning rating (r = -0.108, p = 0.000). Significant associations were also found between sleep quality and both the IFQ score (r = -0.209, p = 0.000) and 1-item perceived immune functioning rating (r = 0.199, p = 0.000). Conclusion: Significant associations were observed between perceived immune functioning and various sleep parameters. These results confirm previous findings of a bi-directional relationship between sleep and immune functioning, and suggest that a healthy immune status may contribute to improved sleep, and vice versa
Analysis of an immunodominant region of infectious bronchitis virus
No full textWe analyzed the antigenic fine-structure of an immunodominant region in the peplomer protein of infectious bronchitis virus. This region near the N-terminus of the S2 subunit is recognized by polyclonal antisera and by the majority of mAb that cross-react with denatured protein. Despite their involvement in neutralization, epitopes in this region were conserved in different serotypes. Epitopes of four mAb and two chicken antisera were localized by using prokaryotic expression of cDNA fragments, and overlapping peptides with lengths increasing from 3 to 12 residues (PEPSCAN). We found overlapping epitopes with lengths of 6, 9, 11, and more than 17 residues. The results indicate that the expression products are antigenically equivalent to denatured protein fragments. This suggests a general strategy for the localization of sequential epitopes in large proteins. We propose that the immunodominance of the N-terminal region of S2 is explained by features of the protein structure. Presumably, this region is a protruding protein segment of about 20 residues with a high local mobility, as indicated by the antigenicity of the peptides. The conservation of the sequence points to an involvement in a molecular recognition process during infection
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