Acetylcholinesterase Cdna Sequencing And Identification Of Mutations Associated With Organophosphate Resistance In Cochliomyia Hominivorax (diptera: Calliphoridae)

Altered acetylcholinesterase (AChE) has been identified in numerous arthropod species resistant to organophosphate (OP) and carbamate insecticides. The New World screwworm (NWS) Cochliomyia hominivorax (Coquerel), one of the most important myiasis-causing flies in the Neotropics, has been controlled mainly by the application of OP insecticides in its current geographical distribution. However, few studies have investigated insecticide resistance in this species. Based on previous studies about mutations conferring OP resistance in related dipteran species, AChE cDNA was sequenced allowing a survey for mutations (I298V, G401A, F466Y) in NWS populations. In addition, the G137D mutation in the carboxylesterase E3 gene, also associated with OP resistance, was analyzed in the same NWS populations. Only 2/135 individuals presented an altered AChE gene (F466Y). In contrast, a high frequency of the G137D mutation in the E3 gene was found in some localities of Brazil and Uruguay, while the mutant allele was not found in Cuba, Venezuela or Colombia. These findings suggest that the alteration in the carboxylesterase E3 gene may be one of the main resistance mechanisms selected in this ectoparasite. The knowledge of the frequency of these resistance-associated mutations in the NWS natural populations may contribute to the selection of appropriate chemicals for control as part of pest management strategies. © 2010 Elsevier B.V.17701/02/15190195Altschul, S.F., Maden, T.L., Schäffer, A.A., Zhang, Z., Miller, W., Lipman, D.J., Gapped BLAST and PSI-BLAST: a new generation of protein database search programs (1997) Nucleic Acids Res., 25, pp. 3389-3402Bendtsen, J.D., Nielsen, H., von Heijne, G., Brunak, S., Improved prediction of signal peptides: signal P 3.0 (2004) J. Mol. 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Evolving concepts on the pathophysiology of generalised absence seizures: the cortical focus theory

Item does not contain fulltextThree major theories concerning the pathophysiology of generalised absence seizures have been proposed. Penfield and Jasper (1947) put forward the 'centrencephalic' theory, suggesting that the discharges originate from a deep-seated central subcortical pacemaker in the midline thalamus, which diffusely projects to the cortex. This concept was refined by Buzsáki (1991) who proposed that the reticular thalamic nucleus contains the pacemaker cells for the thalamic clock, which imposes its rhythm to the cortex. According to proponents of the cortical theory (Gibbs and Gibbs, 1952; Bancaud, 1969; Lüders et al., 1984; Niedermeyer, 1969), however, the cortex plays a leading role. They found evidence that generalised spike-wave discharges have a focal onset in the frontal cortex. They suggested that seizures became secondarily generalised through a rapid propagation over the cortex. The cortico-reticular theory, postulated by Gloor (1968), formed a reconciliation between the thalamic and cortical theory. Work on the 'feline penicillin generalised epilepsy' model showed that the mechanisms responsible for the spike-wave discharges were linked to the thalamocortical mechanisms that generate spindles. Gloor (1968) demonstrated that rhythmic spindle oscillations generated in the thalamus could be transformed into spike-wave discharges when the cortex was made hyperexcitable. In that case the cortex initiates abnormal hypersynchronous oscillations in the thalamocortical network. Experiments performed in genetically epileptic rats by Meeren et al. (2002) confirmed that a functionally intact thalamocortical network is required for the generation of generalised spike-wave discharges. They investigated the cortico-cortical, intrathalamic and cortico-thalamic interrelationships during spontaneous absence seizures using the advanced signal analysis method of nonlinear association analysis. The analyses revealed a consistent cortical 'focus' within the peri-oral region of the somatosensory cortex. From here, seizure activity spreads rapidly over the cortex, which gives the discharges their generalized appearance. During the first few cycles of the seizure the cortex drives the thalamus, which subsequently becomes entrained into the oscillation. Thereafter cortex and thalamus form a unified network in which both structures drive each other, thus amplifying and maintaining the rhythmic paroxysmal discharges. In this way Meeren's et al. (2002) cortical focus theory for generalised absence epilepsy forms a synthesis between the cortical and the cortico-reticular theory

Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory

Contains fulltext : 55480.pdf (publisher's version ) (Closed access)Four main theories on the pathophysiology of generalized absence seizures have been proposed. The "centrencephalic" theory, proposed in 1954, suggested that discharges originate from a deep-seated diffusely projecting subcortical pacemaker in the midline thalamus. This concept was refined in 1991 with the "thalamic clock". theory, implying that the reticular thalamic nucleus contains the pacemaker cells for the thalamic clock, imposing its rhythm to the cortex. According to other investigators, however, the cortex seems to play a leading role. They suggested that spike-wave discharges have a focal onset in the cortex and are generalized through a rapid propagation. In the "corticoreticular" theory, postulated in 1968, spike-wave discharges are linked to the thalamocortical mechanisms that generate spindles. Rhythmic spindle oscillations generated in the thalamus are transformed into spike-wave discharges when the cortex is hyperexcitable. A 2002 study confirmed in epileptic rats that a functionally intact thalamocortical network is required for the generation of spike-wave discharges. The corticothalamic interrelationships were investigated by means of nonlinear association signal analyses of multiple spike-wave discharges. This showed a consistent focus within the perioral region of the somatosensory cortex. From this focus, seizure activity generalizes rapidly over the cortex. During the first cycles of the seizure the cortex drives the thalamus, while thereafter cortex and thalamus drive each other, thus amplifying and maintaining the rhythmic discharge. In this way the "cortical focus" theory for generalized absence epilepsy bridges cortical and thalamic theories

Evolving concepts on the pathophysiology of generalised absence seizures: the cortical focus theory

Three major theories concerning the pathophysiology of generalised absence seizures have been proposed. Penfield and Jasper (1947) put forward the 'centrencephalic' theory, suggesting that the discharges originate from a deep-seated central subcortical pacemaker in the midline thalamus, which diffusely projects to the cortex. This concept was refined by Buzsáki (1991) who proposed that the reticular thalamic nucleus contains the pacemaker cells for the thalamic clock, which imposes its rhythm to the cortex. According to proponents of the cortical theory (Gibbs and Gibbs, 1952; Bancaud, 1969; Lüders et al., 1984; Niedermeyer, 1969), however, the cortex plays a leading role. They found evidence that generalised spike-wave discharges have a focal onset in the frontal cortex. They suggested that seizures became secondarily generalised through a rapid propagation over the cortex. The cortico-reticular theory, postulated by Gloor (1968), formed a reconciliation between the thalamic and cortical theory. Work on the 'feline penicillin generalised epilepsy' model showed that the mechanisms responsible for the spike-wave discharges were linked to the thalamocortical mechanisms that generate spindles. Gloor (1968) demonstrated that rhythmic spindle oscillations generated in the thalamus could be transformed into spike-wave discharges when the cortex was made hyperexcitable. In that case the cortex initiates abnormal hypersynchronous oscillations in the thalamocortical network. Experiments performed in genetically epileptic rats by Meeren et al. (2002) confirmed that a functionally intact thalamocortical network is required for the generation of generalised spike-wave discharges. They investigated the cortico-cortical, intrathalamic and cortico-thalamic interrelationships during spontaneous absence seizures using the advanced signal analysis method of nonlinear association analysis. The analyses revealed a consistent cortical 'focus' within the peri-oral region of the somatosensory cortex. From here, seizure activity spreads rapidly over the cortex, which gives the discharges their generalized appearance. During the first few cycles of the seizure the cortex drives the thalamus, which subsequently becomes entrained into the oscillation. Thereafter cortex and thalamus form a unified network in which both structures drive each other, thus amplifying and maintaining the rhythmic paroxysmal discharges. In this way Meeren's et al. (2002) cortical focus theory for generalised absence epilepsy forms a synthesis between the cortical and the cortico-reticular theory

Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats

Absence seizures are the most pure form of generalized epilepsy. They are characterized in the electroencephalogram by widespread bilaterally synchronous spike-wave discharges (SWDs), which are the reflections of highly synchronized oscillations in thalamocortical networks. To reveal network mechanisms responsible for the initiation and generalization of the discharges, we studied the interrelationships between multisite cortical and thalamic field potentials recorded during spontaneous SWDs in the freely moving WAG/Rij rat, a genetic model of absence epilepsy. Nonlinear association analysis revealed a consistent cortical “focus” within the peri-oral region of the somatosensory cortex. The SWDs recorded at other cortical sites consistently lagged this focal site, with time delays that increased with electrode distance (corresponding to a mean propagation velocity of 1.4 m/sec). Intra-thalamic relationships were more complex and could not account for the observed cortical propagation pattern. Cortical and thalamic sites interacted bi-directionally, whereas the direction of this coupling could vary throughout one seizure. However, during the first 500 msec, the cortical focus was consistently found to lead the thalamus. These findings argue against the existence of one common subcortical pacemaker for the generation of generalized spikewave discharges characteristic for absence seizures in the rat. Instead, the results suggest that a cortical focus is the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops, and that the large-scale synchronization is mediated by ways of an extremely fast intracortical spread of seizure activity. Analogous mechanisms may underlie the pathophysiology of human absence epilepsy