942 resultados para MULTIPLE ACTION MECHANISMS
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"EPA contract no. 68-C8-0062, Work assignment no. 3-48, SAIC project no. 01-0895-03-1000."
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No abstract
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A study has been made of drugs acting at 5-HT receptors on animal models of anxiety. An elevated X-maze was used as a model of anxiety for rats and the actions of various ligands for the 5-HT receptor, and its subtypes, were examined in this model. 5-HT agonists, with varying affinities for the 5-HT receptor subtypes, were demonstrated to have anxiogenic-like activity. The 5-HT2 receptor antagonists ritanserin and ketanserin exhibited an anxiolytic-like profile. The new putatuve anxiolytics ipsapirone and buspirone, which are believed to be selective for 5-HT1 receptors, were also examined. The former had an anxiolytic profile whilst the latter was without effect. Antagonism studies showed the anxiogenic response to 8-hydroxy-2-(Di-n-propylamino)tetralin (8-OH-DPAT) to be antagonised by ipsapirone, pindolol, alprenolol and para-chlorophenylalanine, but not by diazepam, ritanserin, metoprolol, ICI118,551 or buspirone. To confirm some of the results obtained in the elevated X-maze the Social Interaction Test of anxiety was used. Results in this test mirrored the effects seen with the 5-HT agonists, ipsapirone and pindolol, whilst the 5-HT2 receptor antagonists were without effect. Studies using operant conflict models of anxiety produced marginal and varying results which appear to be in agreement with recent criticisms of such models. Finally, lesions of the dorsal raphe nucleus (DRN) were performed in order to investigate the mechanisms involved in the production of the anxiogenic response to 8-OH-DPAT. Overall the results lend support to the involvement of 5-HT, and more precisely 5-HT1, receptors in the manifestation of anxiety in such animal models.
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Sport and exercise psychologists provide some interventions for clients based on limited direct evidence and partial understanding of the mechanisms that underpin their efficacy. The authors review a recent technique, transcranial magnetic stimulation (TMS), which offers a tested procedure for investigating cortical activity during observation and imagery processes. They provide a detailed description of the TMS protocol and highlight some of the key studies that inform sport and exercise psychology research. Finally, the authors offer some thoughts on the direct application to practice.
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Transcranial magnetic stimulation (TMS) studies indicate that the observation of other people's actions influences the excitability of the observer's motor system. Motor evoked potential (MEP) amplitudes typically increase in muscles which would be active during the execution of the observed action. This 'motor resonance' effect is thought to result from activity in mirror neuron regions, which enhance the excitability of the primary motor cortex (M1) via cortico-cortical pathways. The importance of TMS intensity has not yet been recognised in this area of research. Low-intensity TMS predominately activates corticospinal neurons indirectly, whereas high-intensity TMS can directly activate corticospinal axons. This indicates that motor resonance effects should be more prominent when using low-intensity TMS. A related issue is that TMS is typically applied over a single optimal scalp position (OSP) to simultaneously elicit MEPs from several muscles. Whether this confounds results, due to differences in the manner that TMS activates spatially separate cortical representations, has not yet been explored. In the current study, MEP amplitudes, resulting from single-pulse TMS applied over M1, were recorded from the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles during the observation of simple finger abductions. We tested if the TMS intensity (110% vs. 130% resting motor threshold) or stimulating position (FDI-OSP vs. ADM-OSP) influenced the magnitude of the motor resonance effects. Results showed that the MEP facilitation recorded in the FDI muscle during the observation of index-finger abductions was only detected using low-intensity TMS. In contrast, changes in the OSP had a negligible effect on the presence of motor resonance effects in either the FDI or ADM muscles. These findings support the hypothesis that MN activity enhances M1 excitability via cortico-cortical pathways and highlight a methodological framework by which the neural underpinnings of action observation can be further explored. © 2013 Loporto et al.
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The present report reviews behavioural, electroencephalographic, and especially magnetoencephalographic findings on the cortical mechanisms underlying attentional processes that separate targets from distractors and that ensure durable target representations for goal-directed action. A common way of investigation is to observe the system’s overt and covert behaviour when capacity limitations are reached. Here we focus on the aspect of temporally enhanced processing load, namely on performance deficits occurring under rapid-serial-visual-presentation (RSVP) conditions. The most prominent of these deficits is the so-called “attentional blink” (AB) effect. We first report MEG findings with respect to the time course of activation that shows modulations around 300 ms after target onset which reflect demands and success of target consolidation. Then, findings regarding long-range inter-area phase synchronization are reported that are hypothesized to mediate communication within the attentional network. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioural performance. Furthermore, enhanced vigilance of the system elicits systematically increased synchronization indices. A hypothetical framework is sketched out that aims at explaining limitations in multiple target consolidation under RSVP conditions.
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This chapter describes the sites and mechanisms of action of the major groups of microbicides, relating their physical and chemical properties to interactions with microbial structures. It considers the physical, cellular and molecular methods for studying the mechanisms of action of chemical microbicides. These range from the uptake, binding and penetration of microbial cells, to the interaction with microbial structures, including the cell wall, membrane, nucleic acids, cytoplasm and enzymes. Key features of the mechanisms of action of the major groups of microbicides are described covering oxidizing agents, alkylating agents, metal ion-binding agents, nucleic acid-binding agents, protein denaturants and agents that interact with lipids. © 2013 Blackwell Publishing Ltd.
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This research is funded by UK Medical Research Council grant number MR/L011115/1
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This research is funded by UK Medical Research Council grant number MR/L011115/1. We would like to thank the 105 experts in behaviour change who have committed their time and offered their expertise for study 2 of this research. We are also very grateful to all those who sent us peer-reviewed behaviour change intervention descriptions for study 1. Finally, we would like thank Dr. Emma Beard and Dr. Dan Dediu for their statistical input and to all the researchers, particularly Holly Walton, who have assisted in the coding of papers for study 1.
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Multiple myeloma is characterized by genomic alterations frequently involving gains and losses of chromosomes. Single nucleotide polymorphism (SNP)-based mapping arrays allow the identification of copy number changes at the sub-megabase level and the identification of loss of heterozygosity (LOH) due to monosomy and uniparental disomy (UPD). We have found that SNP-based mapping array data and fluorescence in situ hybridization (FISH) copy number data correlated well, making the technique robust as a tool to investigate myeloma genomics. The most frequently identified alterations are located at 1p, 1q, 6q, 8p, 13, and 16q. LOH is found in these large regions and also in smaller regions throughout the genome with a median size of 1 Mb. We have identified that UPD is prevalent in myeloma and occurs through a number of mechanisms including mitotic nondisjunction and mitotic recombination. For the first time in myeloma, integration of mapping and expression data has allowed us to reduce the complexity of standard gene expression data and identify candidate genes important in both the transition from normal to monoclonal gammopathy of unknown significance (MGUS) to myeloma and in different subgroups within myeloma. We have documented these genes, providing a focus for further studies to identify and characterize those that are key in the pathogenesis of myeloma.
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Sheath rot complex and seed discoloration in rice involve a number of pathogenic bacteria that cannot be associated with distinctive symptoms. These pathogens can easily travel on asymptomatic seeds and therefore represent a threat to rice cropping systems. Among the rice-infecting Pseudomonas, P. fuscovaginae has been associated with sheath brown rot disease in several rice growing areas around the world. The appearance of a similar Pseudomonas population, which here we named P. fuscovaginae-like, represents a perfect opportunity to understand common genomic features that can explain the infection mechanism in rice. We showed that the novel population is indeed closely related to P. fuscovaginae. A comparative genomics approach on eight rice-infecting Pseudomonas revealed heterogeneous genomes and a high number of strain-specific genes. The genomes of P. fuscovaginae-like harbor four secretion systems (Type I, II, III, and VI) and other important pathogenicity machinery that could probably facilitate rice colonization. We identified 123 core secreted proteins, most of which have strong signatures of positive selection suggesting functional adaptation. Transcript accumulation of putative pathogenicity-related genes during rice colonization revealed a concerted virulence mechanism. The study suggests that rice-infecting Pseudomonas causing sheath brown rot are intrinsically diverse and maintain a variable set of metabolic capabilities as a potential strategy to occupy a range of environments.