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1.
Neuroimage Clin ; 32: 102814, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34537682

RESUMO

INTRODUCTION: Magnetoencephalography (MEG), allows for a high degree temporal and spatial accuracy in recording cortical oscillatory activity and evoked fields. To date, no review has been undertaken to synthesise all MEG studies in Multiple Sclerosis (MS). We undertook a Systematic Review of the utility of MEG in MS. METHODS: We identified MEG studies carried out in MS using EMBASE, Medline, Cochrane, TRIP and Psychinfo databases. We included original research articles with a cohort of minimum of five multiple sclerosis patients and quantifying of at least one MEG parameter. We used a modified version of the JBI (mJBI) for case-control studies to assess for risk of bias. RESULTS: We identified 30 studies from 13 centres involving at least 433 MS patients and 347 controls. We found evidence that MEG shows perturbed activity (most commonly reduced power modulations), reduced connectivity and association with altered clinical function in Multiple Sclerosis. Specific replicated findings were decreased motor induced responses in the beta band, diminished increase of gamma power after visual stimulation, increased latency and reduced connectivity for somatosensory evoked fields. There was an association between upper alpha connectivity and cognitive measures in people with MS. Overall studies were of moderate quality (mean mJBI score 6.7). DISCUSSION: We find evidence for the utility of MEG in Multiple Sclerosis. Event-related designs are of particular value and show replicability between centres. At this stage, it is not clear whether these changes are specific to Multiple Sclerosis or are also observable in other diseases. Further studies should look to explore cognitive control in more depth using in-task designs and undertake longitudinal studies to determine whether these changes have prognostic value.


Assuntos
Magnetoencefalografia , Esclerose Múltipla , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Estimulação Luminosa
2.
Neuroimage Clin ; 16: 175-183, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28794978

RESUMO

Parkinsonian bradykinesia and rigidity are typically associated with excessive beta band oscillations in the subthalamic nucleus. Recently another spectral peak has been identified that might be implicated in the pathophysiology of the disease: high-frequency oscillations (HFO) within the 150-400 Hz range. Beta-HFO phase-amplitude coupling (PAC) has been found to correlate with severity of motor impairment. However, the neuronal origin of HFO and its usefulness as a potential target for deep brain stimulation remain to be established. For example, it is unclear whether HFO arise from the same neural populations as beta oscillations. We intraoperatively recorded local field potentials from the subthalamic nucleus while advancing DBS electrodes in 2 mm steps from 4 mm above the surgical target point until 2 mm below, resulting in 4 recording sites. Data from 26 nuclei from 14 patients were analysed. For each trajectory, we identified the recording site with the largest spectral peak in the beta range (13-30 Hz), and the largest peak in the HFO range separately. In addition, we identified the recording site with the largest beta-HFO PAC. Recording sites with largest beta power and largest HFO power coincided in 50% of cases. In the other 50%, HFO was more likely to be detected at a more superior recording site in the target area. PAC followed more closely the site with largest HFO (45%) than beta power (27%). HFO are likely to arise from spatially close, but slightly more superior neural populations than beta oscillations. Further work is necessary to determine whether the different activities can help fine-tune deep brain stimulation targeting.


Assuntos
Ritmo beta , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Idoso , Ondas Encefálicas , Estimulação Encefálica Profunda , Humanos , Pessoa de Meia-Idade , Processamento de Sinais Assistido por Computador
3.
Neuroimage ; 146: 355-366, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27871922

RESUMO

Neural models describe brain activity at different scales, ranging from single cells to whole brain networks. Here, we attempt to reconcile models operating at the microscopic (compartmental) and mesoscopic (neural mass) scales to analyse data from microelectrode recordings of intralaminar neural activity. Although these two classes of models operate at different scales, it is relatively straightforward to create neural mass models of ensemble activity that are equipped with priors obtained after fitting data generated by detailed microscopic models. This provides generative (forward) models of measured neuronal responses that retain construct validity in relation to compartmental models. We illustrate our approach using cross spectral responses obtained from V1 during a visual perception paradigm that involved optogenetic manipulation of the basal forebrain. We find that the resulting neural mass model can distinguish between activity in distinct cortical layers - both with and without optogenetic activation - and that cholinergic input appears to enhance (disinhibit) superficial layer activity relative to deep layers. This is particularly interesting from the perspective of predictive coding, where neuromodulators are thought to boost prediction errors that ascend the cortical hierarchy.


Assuntos
Modelos Neurológicos , Neurônios/fisiologia , Córtex Visual/fisiologia , Acetilcolina/fisiologia , Animais , Prosencéfalo Basal/fisiologia , Teorema de Bayes , Humanos , Camundongos , Redes Neurais de Computação
4.
J Neurosci Methods ; 243: 94-102, 2015 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-25677405

RESUMO

BACKGROUND: Growing experimental evidence suggests an important role for cross-frequency coupling in neural processing, in particular for phase-amplitude coupling (PAC). Although the details of methods to detect PAC may vary, a common procedure to estimate the significance level is the comparison of observed values to those of at least 100 surrogate time series. When scanning large parts of the frequency spectrum and multiple recording sites, this could amount to very large computation times. NEW METHOD: We demonstrate that the general linear model (GLM) allows for a parametric estimation of significant PAC. Continuous recordings are split into epochs, of a few seconds duration, on which an F-test can be performed. We compared its performance against traditional non-parametric permutation tests in both simulated and experimental data. RESULTS: Our method was able to reproduce findings of phase-amplitude coupling in local field potential recordings obtained from the subthalamic nucleus in patients with Parkinson's disease. We also show that PAC may be detected between the subthalamic nucleus and cortical motor areas. COMPARISON WITH EXISTING METHOD(S): Although the GLM slightly underestimated significance compared to permutation tests in the simulations, for experimental data the two methods produced highly similar results. Computation times were drastically lower for the GLM. Furthermore, we demonstrate that the GLM can be easily extended by including additional predictors such as low-frequency amplitude to test for amplitude-amplitude coupling. CONCLUSIONS: The GLM forms an adequate and computationally efficient approach for detecting cross-frequency coupling with the flexibility to add other explanatory variables of interest.


Assuntos
Modelos Lineares , Processamento de Sinais Assistido por Computador , Antiparkinsonianos/uso terapêutico , Simulação por Computador , Estimulação Encefálica Profunda/métodos , Humanos , Magnetoencefalografia/métodos , Córtex Motor/efeitos dos fármacos , Córtex Motor/fisiopatologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Núcleo Subtalâmico/efeitos dos fármacos , Núcleo Subtalâmico/fisiopatologia , Fatores de Tempo
5.
Neuroimage ; 108: 460-75, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25585017

RESUMO

This paper reports a dynamic causal modeling study of electrocorticographic (ECoG) data that addresses functional asymmetries between forward and backward connections in the visual cortical hierarchy. Specifically, we ask whether forward connections employ gamma-band frequencies, while backward connections preferentially use lower (beta-band) frequencies. We addressed this question by modeling empirical cross spectra using a neural mass model equipped with superficial and deep pyramidal cell populations-that model the source of forward and backward connections, respectively. This enabled us to reconstruct the transfer functions and associated spectra of specific subpopulations within cortical sources. We first established that Bayesian model comparison was able to discriminate between forward and backward connections, defined in terms of their cells of origin. We then confirmed that model selection was able to identify extrastriate (V4) sources as being hierarchically higher than early visual (V1) sources. Finally, an examination of the auto spectra and transfer functions associated with superficial and deep pyramidal cells confirmed that forward connections employed predominantly higher (gamma) frequencies, while backward connections were mediated by lower (alpha/beta) frequencies. We discuss these findings in relation to current views about alpha, beta, and gamma oscillations and predictive coding in the brain.


Assuntos
Retroalimentação Fisiológica , Haplorrinos/fisiologia , Córtex Visual/fisiologia , Animais , Modelos Teóricos , Rede Nervosa/fisiologia
7.
Neuroimage ; 103: 181-191, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25241908

RESUMO

We tested whether mirror visual feedback (MVF) from a moving hand induced high gamma oscillation (HGO) response in the hemisphere contralateral to the mirror and ipsilateral to the self-paced movement. MEG was recorded in 14 subjects under three conditions: bilateral synchronous movements of both index fingers (BILATERAL), movements of the right hand index finger while observing the immobile left index finger (NOMIRROR), and movements of the right hand index finger while observing its mirror reflection (MIRROR). The right hemispheric spatiospectral regions of interests (ROIs) in the sensor space, sensitive to bilateral movements, were found by statistical comparison of the BILATERAL spectral responses to baseline. For these ROIs, the post-movement HGO responses were compared between the MIRROR and NOMIRROR conditions. We found that MVF from the moving hand, similarly to the real movements of the opposite hand, induced HGOs (55-85Hz) in the sensorimotor cortex. This MVF effect was frequency-specific and did not spread to oscillations in other frequency bands. This is the first study demonstrating movement-related HGO induced by MVF from the moving hand in the absence of proprioceptive feedback signaling. Our findings support the hypothesis that MVF can trigger the feedback-based control processes specifically associated with perception of one's own movements.


Assuntos
Encéfalo/fisiologia , Potenciais Evocados Visuais/fisiologia , Ritmo Gama/fisiologia , Ilusões Ópticas/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Lateralidade Funcional/fisiologia , Mãos/fisiologia , Humanos , Magnetoencefalografia , Masculino , Movimento/fisiologia , Adulto Jovem
8.
Neuroimage ; 92: 143-55, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24495812

RESUMO

Using high-density electrocorticographic recordings - from awake-behaving monkeys - and dynamic causal modelling, we characterised contrast dependent gain control in visual cortex, in terms of synaptic rate constants and intrinsic connectivity. Specifically, we used neural field models to quantify the balance of excitatory and inhibitory influences; both in terms of the strength and spatial dispersion of horizontal intrinsic connections. Our results allow us to infer that increasing contrast increases the sensitivity or gain of superficial pyramidal cells to inputs from spiny stellate populations. Furthermore, changes in the effective spatial extent of horizontal coupling nuance the spatiotemporal filtering properties of cortical laminae in V1 - effectively preserving higher spatial frequencies. These results are consistent with recent non-invasive human studies of contrast dependent changes in the gain of pyramidal cells elaborating forward connections - studies designed to test specific hypotheses about precision and gain control based on predictive coding. Furthermore, they are consistent with established results showing that the receptive fields of V1 units shrink with increasing visual contrast.


Assuntos
Conectoma/métodos , Sensibilidades de Contraste/fisiologia , Modelos Neurológicos , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Células Piramidais/fisiologia , Córtex Visual/fisiologia , Animais , Atenção/fisiologia , Simulação por Computador , Eletroencefalografia/métodos , Macaca mulatta , Masculino , Campos Visuais/fisiologia
9.
Neuroimage ; 84: 476-87, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24041874

RESUMO

The MEG/EEG inverse problem is ill-posed, giving different source reconstructions depending on the initial assumption sets. Parametric Empirical Bayes allows one to implement most popular MEG/EEG inversion schemes (Minimum Norm, LORETA, etc.) within the same generic Bayesian framework. It also provides a cost-function in terms of the variational Free energy-an approximation to the marginal likelihood or evidence of the solution. In this manuscript, we revisit the algorithm for MEG/EEG source reconstruction with a view to providing a didactic and practical guide. The aim is to promote and help standardise the development and consolidation of other schemes within the same framework. We describe the implementation in the Statistical Parametric Mapping (SPM) software package, carefully explaining each of its stages with the help of a simple simulated data example. We focus on the Multiple Sparse Priors (MSP) model, which we compare with the well-known Minimum Norm and LORETA models, using the negative variational Free energy for model comparison. The manuscript is accompanied by Matlab scripts to allow the reader to test and explore the underlying algorithm.


Assuntos
Algoritmos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Eletroencefalografia/métodos , Interpretação de Imagem Assistida por Computador/métodos , Magnetoencefalografia/métodos , Reconhecimento Automatizado de Padrão/métodos , Inteligência Artificial , Teorema de Bayes , Interpretação Estatística de Dados , Humanos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Neuroimage ; 71: 104-13, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23313570

RESUMO

We demonstrate the capacity of dynamic causal modeling to characterize the nonlinear coupling among cortical sources that underlie time-frequency modulations in MEG data. Our experimental task involved the mental rotation of hand drawings that ten subjects used to decide if it was a right or left hand. Reaction times were shorter when the stimuli were presented with a small rotation angle (fast responses) compared to a large rotation angle (slow responses). The grand-averaged data showed that in both cases performance was accompanied by a marked increase in gamma activity in occipital areas and a concomitant decrease in alpha and beta power in occipital and motor regions. Modeling directed (cross) frequency interactions between the two regions revealed that after the stimulus induced a gamma increase and beta decrease in occipital regions, interactions with the motor area served to attenuate these modulations. The difference between fast and slow behavioral responses was manifest as an altered coupling strength in both forward and backward connections, which led to a less pronounced attenuation for more difficult (slow reaction time) trials. This was mediated by a (backwards) beta to gamma coupling from motor till occipital sources, whereas other interactions were mainly within the same frequency. Results are consistent with the theory of predictive coding and suggest that during motor imagery, the influence of motor areas on activity in occipital cortex co-determines performance. Our study illustrates the benefit of modeling experimental responses in terms of a generative model that can disentangle the contributions of intra-areal vis-à-vis inter-areal connections to time-frequency modulations during task performance.


Assuntos
Imaginação/fisiologia , Modelos Neurológicos , Córtex Motor/fisiologia , Vias Neurais/fisiologia , Lobo Occipital/fisiologia , Algoritmos , Humanos , Magnetoencefalografia , Dinâmica não Linear , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia
11.
Neuroimage ; 66: 563-76, 2013 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23128079

RESUMO

This paper presents a dynamic causal model based upon neural field models of the Amari type. We consider the application of these models to non-invasive data, with a special focus on the mapping from source activity on the cortical surface to a single channel. We introduce a neural field model based upon the canonical microcircuit (CMC), in which neuronal populations are assigned to different cortical layers. We show that DCM can disambiguate between alternative (neural mass and field) models of cortical activity. However, unlike neural mass models, DCM with neural fields can address questions about neuronal microcircuitry and lateral interactions. This is because they are equipped with interlaminar connections and horizontal intra-laminar connections that are patchy in nature. These horizontal or lateral connections can be regarded as connecting macrocolumns with similar feature selectivity. Crucially, the spatial parameters governing horizontal connectivity determine the separation (width) of cortical macrocolumns. Thus we can estimate the width of macro columns, using non-invasive electromagnetic signals. We illustrate this estimation using dynamic causal models of steady-state or ongoing spectral activity measured using magnetoencephalography (MEG) in human visual cortex. Specifically, we revisit the hypothesis that the size of a macrocolumn is a key determinant of neuronal dynamics, particularly the peak gamma frequency. We are able to show a correlation, over subjects, between columnar size and peak gamma frequency - that fits comfortably with established correlations between peak gamma frequency and the size of visual cortex defined retinotopically. We also considered cortical excitability and assessed its relative influence on observed gamma activity. This example highlights the potential utility of dynamic causal modelling and neural fields in providing quantitative characterisations of spatially extended dynamics on the cortical surface - that are parameterised in terms of horizontal connections, implicit in the cortical micro-architecture and its synaptic parameters.


Assuntos
Algoritmos , Mapeamento Encefálico , Modelos Neurológicos , Córtex Visual/fisiologia , Simulação por Computador , Humanos , Magnetoencefalografia
12.
Neuroimage ; 59(1): 439-55, 2012 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-21820062

RESUMO

This note describes an extension of Bayesian model inversion procedures for the Dynamic Causal Modeling (DCM) of complex-valued data. Modeling complex data can be particularly useful in the analysis of multivariate ergodic (stationary) time-series. We illustrate this with a generalization of DCM for steady-state responses that models both the real and imaginary parts of sample cross-spectra. DCM allows one to infer underlying biophysical parameters generating data (like synaptic time constants, connection strengths and conduction delays). Because transfer functions and complex cross-spectra can be generated from these parameters, one can also describe the implicit system architecture in terms of conventional (linear systems) measures; like coherence, phase-delay or cross-correlation functions. Crucially, these measures can be derived in both sensor and source-space. In other words, one can examine the cross-correlation or phase-delay functions between hidden neuronal sources using non-invasive data and relate these functions to synaptic parameters and neuronal conduction delays. We illustrate these points using local field potential recordings from the subthalamic nucleus and globus pallidus, with a special focus on the relationship between conduction delays and the ensuing phase relationships and cross-correlation time lags between population activities.


Assuntos
Algoritmos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Modelos Neurológicos , Modelos Teóricos , Teorema de Bayes , Humanos
13.
J Neurosci Methods ; 183(1): 19-30, 2009 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-19576931

RESUMO

This paper presents an extension of the Dynamic Causal Modelling (DCM) framework to the analysis of phase-coupled data. A weakly coupled oscillator approach is used to describe dynamic phase changes in a network of oscillators. The use of Bayesian model comparison allows one to infer the mechanisms underlying synchronization processes in the brain. For example, whether activity is driven by master-slave versus mutual entrainment mechanisms. Results are presented on synthetic data from physiological models and on MEG data from a study of visual working memory.


Assuntos
Encéfalo/fisiologia , Modelos Biológicos , Neurônios/fisiologia , Dinâmica não Linear , Simulação por Computador , Sincronização Cortical , Humanos , Magnetoencefalografia , Memória de Curto Prazo/fisiologia , Rede Nervosa
14.
Eur J Neurosci ; 28(8): 1686-95, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18657185

RESUMO

It is unclear how subthalamic nucleus activity is modulated by the cerebral cortex. Here we investigate the effect of transcranial magnetic stimulation (TMS) of the cortex on oscillatory subthalamic local field potential activity in the 8-35 Hz (alpha/beta) band, as exaggerated synchronization in this band is implicated in the pathophysiology of parkinsonism. We studied nine patients with Parkinson's disease (PD) to test whether cortical stimulation can modulate synchronized oscillations in the human subthalamic nucleus. With patients at rest, single-pulse TMS was delivered every 5 s over each primary motor area and supplementary motor area at intensities of 85-115% resting motor threshold. Subthalamic local field potentials were recorded from deep brain stimulation electrodes implanted into this nucleus for the treatment of PD. Motor cortical stimulation suppressed beta activity in the subthalamic nucleus from approximately 0.2 to 0.6 s after TMS (repeated measures anova; main effect of time, P < 0.01; main effect of side, P = 0.03), regardless of intensity. TMS over the supplementary motor area also reduced subthalamic beta activity at 95% (P = 0.05) and 115% resting motor threshold (P = 0.01). The oscillatory activity decreased to 80 +/- 26% of baseline (averaged across sites and stimulation intensities). Suppression with subthreshold stimuli confirmed that these changes were centrally driven and not due to peripheral afference. The results may have implications for mechanisms underlying the reported therapeutic benefits of cortical stimulation.


Assuntos
Ritmo beta , Relógios Biológicos/fisiologia , Córtex Motor/fisiologia , Inibição Neural/fisiologia , Núcleo Subtalâmico/fisiologia , Estimulação Magnética Transcraniana/métodos , Potenciais de Ação/fisiologia , Idoso , Estimulação Encefálica Profunda , Eletrodos Implantados , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/anatomia & histologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Núcleo Subtalâmico/anatomia & histologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-16252673

RESUMO

Interaction of pentafluoropyridine with hydroxyl groups of thymidine, uridine, adenosine, and deoxyadenosine at room temperature leads to the formation of aryl ethers of nucleosides with a high yield. Under severe conditions, one more tetrafluoropyridine residue is attached to pyrimidine fragments of T and U, while purine heterocycle in A remains intact. Nucleoside derivatives are formed with a quantitative yield and can be used in situ as intermediates for, as an example, molecular design of arene analogs of nucleic acids. The reaction with thymidine is a successive-parallel process, the limited stage being arylation of the secondary hydroxyl group. The presence of the vicinal hydroxyl group in pentose results in the opposite rate ratio of the formation of primary and secondary tetrafluoropyridyl ethers of adenine and uridine.


Assuntos
Nucleosídeos/química , Piridinas/química , Bioquímica/métodos , Cinética , Espectroscopia de Ressonância Magnética , Timidina/química
16.
Nucleosides Nucleotides Nucleic Acids ; 23(6-7): 849-53, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15560071

RESUMO

o-Bromobenzoic acid was found to promote copper-dependent reactive oxygen species formation from molecular oxygen, resulting in DNA base modification and backbone cleavage. The oligonucleotide conjugate bearing 5-(4'-aminopropyl-sulfomoyl)-2-bromobenzoic acid as a reactive group was synthesized and DNA cleavage activity of this oligonucleotide conjugate was tested on a model deoxyoligonucleotide.


Assuntos
Bromobenzoatos/química , Cobre/química , DNA/química , Oligonucleotídeos/química , Sequência de Bases , Eletroforese em Gel de Poliacrilamida , Hidrólise , Cinética , Oxirredução
17.
Bioorg Khim ; 30(4): 375-82, 2004.
Artigo em Russo | MEDLINE | ID: mdl-15469011

RESUMO

The interaction of 3',5'-bis-O-(alpha,beta,alpha',beta'-tetrafluoropyrid-gamma-yl)thymidine with various nucleophilic reagents was studied to evaluate the possibility of molecular design of new types of nucleic acid analogues using SNAr reactions. The reactions with morpholine and sodium azide led to the introduction of one and two nucleophilic residues into each of the polyfluorinated pyridine rings. The nucleophilic polycondensation with bifunctional reagents ethylenediamine and hexamethylenediamine depended on the nature of nucleophile and reaction conditions and resulted in the formation of supramolecules containing about five or more than 20 pyrimidine bases.


Assuntos
Diaminas/química , Etilenodiaminas/química , Morfolinas/química , Piridinas/química , Azida Sódica/química , Timidina/análogos & derivados , Timidina/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrofotometria Ultravioleta
18.
Bioorg Khim ; 30(1): 54-60, 2004.
Artigo em Russo | MEDLINE | ID: mdl-15040304

RESUMO

Pentafluoropyridine reacts with thymidine, adenosine, and uridine hydroxy groups to give quantitative yields of the corresponding nucleoside di- and triaryl ethers. The nucleophilic substitution reactions proceed successively and in parallel, with the slowest step being the nucleophilic substitution of the nucleoside secondary hydroxyls. The resulting ethers contain tetrafluoropyridyl moieties, which could be smoothly modified by nucleophilic substitution of fluorine atoms. The ethers are useful intermediate synthons (both isolated and in situ) for molecular design of oligonucleotide analogues. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.


Assuntos
Lisina/química , Ácidos Nucleicos/química , Nucleosídeos/química , Polinucleotídeos/química , Piridinas/química , Desenho de Fármacos , Ressonância Magnética Nuclear Biomolecular , Ácidos Nucleicos/síntese química
19.
Artigo em Inglês | MEDLINE | ID: mdl-14565472

RESUMO

We have found, that the reaction of o-bromobenzoic acid with Cu2+ ions can be used as a source of activated oxygen species capable of cleaving DNA. Possibility to apply this reaction for footprinting the nucleosome core in the reconstituted chromatin was demonstrated.


Assuntos
Pegada de DNA/métodos , DNA/química , Proteínas/química , Sítios de Ligação , Hidrólise , Indicadores e Reagentes , Nucleossomos/química , Nucleossomos/genética
20.
Bioorg Khim ; 29(6): 632-9, 2003.
Artigo em Russo | MEDLINE | ID: mdl-14743538

RESUMO

DNA was found to be cleaved in neutral solutions containing arenes and copper (II) salts. The reaction is comparable in efficiency with the DNA cleavage by such systems as Cu(II)-phenanthroline and Cu(II)-ascorbic acid, but, in contrast to the latter, the system Cu(2+)-arene does not require the presence of an exogenous reducing agent or hydrogen peroxide. The system Cu(2+)-arene does not cleave DNA under anaerobic conditions. Catalase, sodium azide, and bathocuproine, which is a specific chelator of Cu(I), completely inhibit the reaction. The data obtained allow one to suppose that Cu(I) ions, superoxide radical, and singlet oxygen participate in the reaction. It has been shown by the EPR method using spin traps that the reaction proceeds with formation of alkoxyl radicals, which can insert breaks in the DNA molecule. For effective cleavage of DNA in the Cu(II)-o-bromobenzoic acid system, the radicals have to be generated by a specific copper-DNA-o-bromobenzoic acid complex, in which copper ions are most probably coordinated with oxygen atoms of the DNA phosphate groups. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2003, vol. 29, no. 6; see also http://www.maik.ru.


Assuntos
Cobre/química , DNA/química , Hidrocarbonetos/química , Catálise , Espectroscopia de Ressonância de Spin Eletrônica , Hidrólise
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