Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.854
Filtrar
1.
J Phys Chem Lett ; 11(12): 4897-4900, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32478523

RESUMO

SARS-CoV-2, since emerging in Wuhan, China, has been a major concern because of its high infection rate and has left more than six million infected people around the world. Many studies endeavored to reveal the structure of the SARS-CoV-2 compared to the SARS-CoV, in order to find solutions to suppress this high infection rate. Some of these studies showed that the mutations in the SARS-CoV spike (S) protein might be responsible for its higher affinity to the ACE2 human cell receptor. In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2. In addition, our results indicate that the enhancement in the binding energy is not due to a single mutant but rather because of the sophisticated structural changes induced by all these mutations together. This finding suggests that it is implausible for the SARS-CoV-2 to be a lab-engineered virus.


Assuntos
Betacoronavirus/química , Receptor Tipo 2 de Angiotensina/química , Vírus da SARS/química , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Simulação por Computador , Infecções por Coronavirus , Fenômenos Eletrofisiológicos , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Método de Monte Carlo , Mutação/genética , Pandemias , Pneumonia Viral , Receptor Tipo 2 de Angiotensina/efeitos dos fármacos , Receptor Tipo 2 de Angiotensina/genética , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/genética
2.
J Med Life ; 13(1): 102-106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341710

RESUMO

Children suffering from conductive or mixed hearing loss may benefit from a bone-anchored hearing aid system (BAHA Attract implantable prosthesis). After audiological rehabilitation, different aspects of development are improving. The objective of this case report is to propose a comprehensive framework for monitoring cortical auditory function after implantation of a bone-anchored hearing aid system by using electrophysiological and neuropsychological measurements. We present the case of a seven-year-old boy with a congenital hearing loss due to a plurimalformative syndrome, including outer and middle ear malformation. After the diagnosis of hearing loss and the audiological rehabilitation with a BAHA Attract implantable prosthesis, the cortical auditory evoked potentials were recorded. We performed a neuropsychological evaluation using the Wechsler Intelligence Scale for Children - Fourth Edition, which was applied according to a standard procedure. The P1 latency was delayed according to the age (an objective biomarker for quantifying cortical auditory function). The neuropsychological evaluation revealed that the child's working memory and verbal reasoning abilities were in the borderline range comparing with his nonverbal reasoning abilities and processing abilities, which were in the average and below-average range, respectively. Cortical auditory evoked potentials, along with neuropsychological evaluation, could be an essential tool for monitoring cortical auditory function in children with hearing loss after a bone-anchored hearing aid implantation.


Assuntos
Córtex Auditivo/fisiologia , Fenômenos Eletrofisiológicos , Auxiliares de Audição , Criança , Orelha Externa/anormalidades , Orelha Externa/fisiopatologia , Potenciais Evocados/fisiologia , Humanos , Anormalidades Maxilomandibulares/fisiopatologia , Masculino , Microstomia/fisiopatologia
3.
Arq Bras Cardiol ; 114(2): 275-280, 2020 02.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32215498

RESUMO

BACKGROUND: The risk of cardiovascular events and sudden death increases with type 1 diabetes mellitus (T1DM). OBJECTIVE: To evaluate electrocardiographic markers of arrhythmias in T1DM patients. METHODS: Electrocardiographic parameters reflecting ventricular depolarization and repolarization, namely, QT, QTc, QTd, QTdc, Tp-e, JT, and JTc intervals and Tp-e/QT and Tp-e/QTc ratios, of 46 patients diagnosed with T1DM were retrospectively analyzed and compared with 46 healthy age-, sex-, and body mass-matched controls. Correlations between T1DM duration, hemoglobin A1c (HbA1c), and ventricular repolarization variables were analyzed. P values lower than 0.05 were considered statistically significant. RESULTS: Diabetes duration was 16.6 ± 7.1 years, and HbA1c was 10.81% ± 3.27% in the T1DM group. In comparison with the control group, heart rate, QTc, QTd, QTdc, Tp-e and JTc intervals, Tp-e/QT ratio (p < 0.001), and Tp-e/QTc ratio (p = 0.007) were significantly higher in T1DM patients. T1DM duration and HbA1c levels were significantly correlated with QTc, QTd, QTdc, Tp-e, and JTc intervals and Tp-e/QT and Tp-e/QTc ratios. CONCLUSIONS: In T1DM patients, potential electrocardiographic repolarization predictors were significantly increased in correlation with disease duration and HbA1c levels. These findings may contribute to the understanding of sudden cardiac death in patients with T1DM.


Assuntos
Arritmias Cardíacas/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Adulto , Estudos de Casos e Controles , Morte Súbita Cardíaca , Eletrocardiografia/métodos , Fenômenos Eletrofisiológicos/fisiologia , Feminino , Hemoglobina A Glicada/análise , Frequência Cardíaca , Humanos , Masculino , Valores de Referência , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo
4.
Phys Chem Chem Phys ; 22(13): 6848-6860, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32195493

RESUMO

Interactions of proteins with functional groups are key to their biological functions, making it essential that they be accurately modeled. To investigate the impact of the inclusion of explicit treatment of electronic polarizability in force fields on protein-functional group interactions, the additive CHARMM and Drude polarizable force field are compared in the context of the Site-Identification by Ligand Competitive Saturation (SILCS) simulation methodology from which functional group interaction patterns with five proteins for which experimental binding affinities of multiple ligands are available, were obtained. The explicit treatment of polarizability produces significant differences in the functional group interactions in the ligand binding sites including overall enhanced binding of functional groups to the proteins. This is associated with variations of the dipole moments of solutes representative of functional groups in the binding sites relative to aqueous solution with higher dipole moments systematically occurring in the latter, though exceptions occur with positively charged methylammonium. Such variation indicates the complex, heterogeneous nature of the electronic environments of ligand binding sites and emphasizes the inherent limitation of fixed charged, additive force fields for modeling ligand-protein interactions. These effects yield more defined orientation of the functional groups in the binding pockets and a small, but systematic improvement in the ability of the SILCS method to predict the binding orientation and relative affinities of ligands to their target proteins. Overall, these results indicate that the physical model associated with the explicit treatment of polarizability along with the presence of lone pairs in a force field leads to changes in the nature of the interactions of functional groups with proteins versus that occurring with additive force fields, suggesting the utility of polarizable force fields in obtaining a more realistic understanding of protein-ligand interactions.


Assuntos
Fenômenos Eletrofisiológicos , Ligação Proteica/fisiologia , Proteínas/química , Sítios de Ligação , Ligantes
5.
PLoS Negl Trop Dis ; 14(3): e0007719, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126087

RESUMO

The putative vector of trachoma, Musca sorbens, prefers to lay its eggs on human faeces on the ground. This study sought to determine whether M. sorbens females were attracted to volatile odours from human faeces in preference to odours from the faeces of other animals, and to determine whether specific volatile semiochemicals mediate selection of the faeces. Traps baited with the faeces of humans and local domestic animals were used to catch flies at two trachoma-endemic locations in The Gambia and one in Ethiopia. At all locations, traps baited with faeces caught more female M. sorbens than control traps baited with soil, and human faeces was the most successful bait compared with soil (mean rate ratios 44.40, 61.40, 10.50 [P<0.001]; 8.17 for child faeces [P = 0.004]). Odours from human faeces were sampled by air entrainment, then extracts of the volatiles were tested by coupled gas chromatography-electroantennography with laboratory-reared female M. sorbens. Twelve compounds were electrophysiologically active and tentatively identified by coupled mass spectrometry-gas chromatography, these included cresol, indole, 2-methylpropanoic acid, butanoic acid, pentanoic acid and hexanoic acid. It is possible that some of these volatiles govern the strong attraction of M. sorbens flies to human faeces. If so, a synthetic blend of these chemicals, at the correct ratios, may prove to be a highly attractive lure. This could be used in odour-baited traps for monitoring or control of this species in trachoma-endemic regions.


Assuntos
Fezes/química , Insetos Vetores/efeitos dos fármacos , Muscidae/efeitos dos fármacos , Feromônios/farmacologia , Compostos Orgânicos Voláteis/farmacologia , Adolescente , Adulto , Animais , Criança , Cromatografia Gasosa , Fenômenos Eletrofisiológicos , Etiópia , Feminino , Gâmbia , Humanos , Insetos Vetores/fisiologia , Masculino , Muscidae/fisiologia , Feromônios/isolamento & purificação , Compostos Orgânicos Voláteis/isolamento & purificação , Adulto Jovem
6.
Nat Neurosci ; 23(3): 398-410, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32066984

RESUMO

In humans and rodents, the perception of control during stressful events has lasting behavioral consequences. These consequences are apparent even in situations that are distinct from the stress context, but how the brain links prior stressful experience to subsequent behaviors remains poorly understood. By assessing innate defensive behavior in a looming-shadow task, we show that the initiation of an escape response is preceded by an increase in the activity of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus (CRHPVN neurons). This anticipatory increase is sensitive to stressful stimuli that have high or low levels of outcome control. Specifically, experimental stress with high outcome control increases CRHPVN neuron anticipatory activity, which increases escape behavior in an unrelated context. By contrast, stress with no outcome control prevents the emergence of this anticipatory activity and decreases subsequent escape behavior. These observations indicate that CRHPVN neurons encode stress controllability and contribute to shifts between active and passive innate defensive strategies.


Assuntos
Hormônio Liberador da Corticotropina/fisiologia , Reação de Fuga/fisiologia , Neurônios/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Estresse Psicológico , Acelerometria , Animais , Antecipação Psicológica/fisiologia , Sinais (Psicologia) , Fenômenos Eletrofisiológicos , Elevação dos Membros Posteriores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Optogenética , Núcleo Hipotalâmico Paraventricular/citologia , Estimulação Luminosa
7.
Nat Cell Biol ; 22(3): 274-281, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32094691

RESUMO

During endoplasmic-reticulum-associated protein degradation (ERAD), misfolded proteins are polyubiquitinated, extracted from the ER membrane and degraded by the proteasome1-4. In a process called retrotranslocation, misfolded luminal proteins first need to traverse the ER membrane before ubiquitination can occur in the cytosol. It was suggested that the membrane-embedded ubiquitin ligase Hrd1 forms a retrotranslocation pore regulated by cycles of auto- and deubiquitination5-8. However, the mechanism by which auto-ubiquitination affects Hrd1 and allows polypeptides to cross the membrane and whether Hrd1 forms a membrane-spanning pore remained unknown. Here, using purified Hrd1 incorporated into different model membranes, we show that Hrd1 auto-ubiquitination leads to the opening of a pore. Substrate binding increases the pore size and its activity, whereas deubiquitination closes the pore and renders it unresponsive to substrate. We identify two binding sites for misfolded proteins in Hrd1, a low-affinity luminal site and a high-affinity cytoplasmic site formed following auto-ubiquitination of specific lysine residues in Hrd1's RING domain. We propose that the affinity difference between the luminal and cytoplasmic binding sites provides the initial driving force for substrate movement through Hrd1.


Assuntos
Degradação Associada com o Retículo Endoplasmático , Dobramento de Proteína , Proteínas de Saccharomyces cerevisiae/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Sítios de Ligação , Carboxipeptidases/metabolismo , Membrana Celular/metabolismo , Fenômenos Eletrofisiológicos , Domínios Proteicos , Transporte Proteico , Proteínas de Saccharomyces cerevisiae/química , Ubiquitina-Proteína Ligases/química
8.
Mar Environ Res ; 155: 104888, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32072990

RESUMO

Electromagnetic surveys generate electromagnetic fields to map petroleum deposits under the seabed with unknown consequences for marine animals. The electric and magnetic fields induced by electromagnetic surveys can be detected by many marine animals, and the generated fields may potentially affect the behavior of perceptive animals. Animals using magnetic cues for migration or local orientation, especially during a restricted time-window, risk being affected by electromagnetic surveys. In electrosensitive animals, anthropogenic electric fields could disrupt a range of behaviors. The lack of studies on effects of the electromagnetic fields induced by electromagnetic surveys on the behavior of magneto- and electrosensitive animals is a reason for concern. Here, we review the use of electric and magnetic fields among marine animals, present data on survey generated and natural electromagnetic fields, and discuss potential effects of electromagnetic surveys on the behavior of marine animals.


Assuntos
Organismos Aquáticos/fisiologia , Campos Eletromagnéticos/efeitos adversos , Fenômenos Eletrofisiológicos , Atividades Humanas , Animais
9.
Medicine (Baltimore) ; 99(5): e19060, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000454

RESUMO

The aim of the study was to evaluate pelvic floor muscle bioelectrical activity in healthy, young, and nulliparous women, and to present normative values for all phases and parameters measured with the Glazer Protocol.In this study, 96 healthy, young, nulliparous women (age 22-27 years; 168.6 ±â€Š5.1 cm; 57.1 ±â€Š11.8 kg) were tested. The bioelectrical activity of the pelvic floor muscles was collected using an endovaginal electrode with the Glazer Protocol, which included the following series of muscles contractions and relaxations: pre-baseline rest, phasic contractions, tonic contractions, isometric contractions for muscle endurance evaluation, and post-baseline rest.The following normative values of the bioelectrical signal for all phases of the Glazer Protocol were calculated: mean, minimal, and maximal values, 95% confidence interval, standard deviation, 95% standard deviation confidence interval, variance, coefficient of variation, and standard error of measurement. Average Mean Amplitude (µV) was as follows: pre-baseline rest (6.26 ±â€Š3.33 µV), phasic contractions (49.76 ±â€Š26.44 µV), tonic contractions (37.05 ±â€Š25.99 µV), endurance contraction (16.10 ±â€Š6.68 µV), and post-baseline rest (6.93 ±â€Š3.99 µV).This study was the first in which normative values for all phases of the Glazer Protocol were reported. This protocol is very often used in electromyography devices as a tool for pelvic floor muscle assessment. Due to the fact that the interpretation of the pelvic floor muscle evaluation is complex and difficult, the authors believe that the normative values proposed in this study allow for comprehensive interpretation of this test (both qualitatively and quantitatively) and provide a reference point for parameters measured in women with different pelvic floor dysfunctions.


Assuntos
Fenômenos Eletrofisiológicos , Diafragma da Pelve/fisiologia , Adulto , Eletromiografia , Feminino , Humanos , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Valores de Referência
10.
J Chem Ecol ; 46(2): 115-127, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32056064

RESUMO

Whittleia retiella (Newman, 1847) is a threatened salt marsh species of the bagworm moth family Psychidae. For its preservation it is necessary to develop efficient tools to survey its distribution and habitat requirements in order to use appropriate conservation methods. Such tools may be pheromone-based monitoring systems, which have documented efficacy in establishing the occurrence of cryptic insect species in nature. By using gas chromatography combined with electroantennographic detection (GC-EAD), we found two compounds in female W. retiella headspace samples and whole-body extracts that elicited electrophysiological activity in male antennae. Gas chromatograpy coupled with mass spectrometry (GC-MS) operating in electron impact (EI) mode and comparison of the analytical data with those of synthetic reference compounds showed the chemical structures of these putative pheromone components to be (1S)-1-methylpropyl (5Z)-dec-5-enoate and 1-methylethyl (5Z)-dec-5-enoate. Field assays using baits loaded with synthetic compounds revealed that conspecific males were attracted to (1S)-1-methylpropyl (5Z)-dec-5-enoate alone or in combination with 1-methylethyl (5Z)-dec-5-enoate, whereas 1-methylethyl (5Z)-dec-5-enoate neither attracted nor repelled males in the field assays when tested alone. This study shows the potential of using (1S)-1-methylpropyl (5Z)-dec-5-enoate for monitoring W. retiella to gather more detailed information about the geographic distribution and habitat needs of this rare moth.


Assuntos
Mariposas/fisiologia , Atrativos Sexuais/química , Animais , Comportamento Animal/efeitos dos fármacos , Fenômenos Eletrofisiológicos , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Atrativos Sexuais/análise , Atrativos Sexuais/farmacologia , Estereoisomerismo , Áreas Alagadas
11.
J Chem Ecol ; 46(2): 176-185, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32062821

RESUMO

Females of the Queensland fruit fly (QFF), Bactrocera tryoni, are amongst the most damaging pests of horticulture in Australia and neighboring countries. Females can lay eggs into more than a hundred species of fruits and vegetables, resulting in large crop losses. Sexually mature males can be managed sustainably with traps baited with long-lasting synthetic lures, and sexually immature males and females can be attracted and killed by short-lived protein baits applied directly on surfaces, with a low success rate (< 20%). No long-lasting attractants for virgin or mated females exist. With the aim of developing a female attractant for surveillance, we collected and analyzed the odors of four ripe host fruits: orange, cherry guava, banana and feijoa. Virgin and mated female QFF were tested with gas-chromatography coupled with electro-antennographic detection to identify electrophysiologically (EAD)-active compounds. We detected 41 EAD-active compounds, with seven found common for more than one fruit. Overall, mated females responded more often and with higher intensity than virgin females. In particular, five compounds present either in cherry guava or feijoa triggered a significantly higher EAD response from mated females than from virgins. Twenty-six EAD-active compounds were selected and tested individually in a Y-tube olfactometer to measure attraction of both virgin and mated females. Behavioral responses differed significantly amongst the compounds, but not strongly between virgin and mated females. We did not find any correlation between electrophysiological and behavioral responses. Further field testing with behaviorally-active compounds is needed for the development of a new QFF female lure.


Assuntos
Odorantes/análise , Tephritidae/fisiologia , Compostos Orgânicos Voláteis/análise , Animais , Antenas de Artrópodes/fisiologia , Comportamento Animal/efeitos dos fármacos , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Feminino , Frutas/química , Frutas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Psidium/química , Psidium/metabolismo , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/farmacologia
12.
PLoS One ; 15(1): e0227274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945080

RESUMO

We examined oscillatory power in electroencephalographic recordings obtained while younger (18-30 years) and older (60+ years) adults studied lists of words for later recall. Power changed in a highly consistent way from word-to-word across the study period. Above 14 Hz, there were virtually no age differences in these neural gradients. But gradients below 14 Hz reliably discriminated between age groups. Older adults with the best memory performance showed the largest departures from the younger adult pattern of neural activity. These results suggest that age differences in the dynamics of neural activity across an encoding period reflect changes in cognitive processing that may compensate for age-related decline.


Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Eletroencefalografia , Transtornos da Memória/fisiopatologia , Rememoração Mental/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Fenômenos Eletrofisiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
13.
Aquat Toxicol ; 220: 105398, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31891816

RESUMO

Recent studies suggest that 2,4-DABA, a neurotoxic excitatory amino acid present in virtually all environments, but predominantly in aquatic ecosystems may be a risk factor for development of neurodegenerative diseases in animals and humans. Despite its neurotoxicity and potential environmental importance, mechanisms underlying the excitatory and putative excitotoxic action of 2,4-DABA in neurons are still unexplored. We previously reported on extensive two-stage membrane depolarization and functional disturbances in leech Retzius neurons induced by 2,4-DABA. Current study presents the first detailed look into the electrophysiological processes leading to this depolarization. Intracellular recordings were performed on Retzius neurons of the leech Haemopis sanguisuga using glass microelectrodes and input membrane resistance (IMR) was measured by injecting hyperpolarizing current pulses through these electrodes. Results show that the excitatory effect 2,4-DABA elicits on neurons' membrane potential is dependent on sodium ions. Depolarizing effect of 5·10-3 mol/L 2,4-DABA in sodium-free solution was significantly diminished by 91% reducing it to 3.26 ±â€¯0.62 mV and its two-stage nature was abrogated. In addition to being sodium-dependent, the depolarization of membrane potential induced by this amino acid is coupled with an increase of membrane permeability, as 2,4-DABA decreases IMR by 8.27 ±â€¯1.47 MΩ (67.60%). Since present results highlight the role of sodium ions, we investigated the role of two putative sodium-dependent mechanisms in 2,4-DABA-induced excitatory effect - activation of ionotropic glutamate receptors and the electrogenic transporter for neutral amino acids. Excitatory effect of 5·10-3 mol/L 2,4-DABA was partially blocked by 10-5 mol/L 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) a non-NMDA receptor antagonist as the first stage of membrane depolarization was significantly reduced by 2.59 ±â€¯0.98 mV (40%), whilst second stage remained unaltered. Moreover, involvement of the sodium-dependent transport system for neutral amino acids was investigated by equimolar co-application of 5·10-3 mol/L 2,4-DABA and L-alanine, a competitive inhibitor of this transporter. Although L-alanine exhibited no effect on the first stage of membrane depolarization elicited by 2,4-DABA, it substantially reduced the second stage (the overall membrane depolarization) from 39.63 ±â€¯2.22 mV to 16.28 ±â€¯2.58 mV, by 58.92%. We therefore propose that the electrophysiological effect of 2,4-DABA on Retzius neurons is mediated by two distinct mechanisms, i.e. by activation of ionotropic glutamate receptor that initiates the first stage of membrane depolarization followed by the stimulation of an electrogenic sodium-dependent neutral amino acid transporter, leading to additional influx of positive charge into the cell and the second stage of depolarization.


Assuntos
Aminobutiratos/toxicidade , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Sanguessugas/fisiologia , Neurônios/efeitos dos fármacos , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Alanina/farmacologia , Sistema A de Transporte de Aminoácidos/antagonistas & inibidores , Animais , Ácido Glutâmico/metabolismo , Sanguessugas/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Neurônios/fisiologia
14.
Nat Commun ; 11(1): 325, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949140

RESUMO

Neuroimaging evidence suggests that the default mode network (DMN) exhibits antagonistic activity with dorsal attention (DAN) and salience (SN) networks. Here we use human intracranial electroencephalography to investigate the behavioral relevance of fine-grained dynamics within and between these networks. The three networks show dissociable profiles of task-evoked electrophysiological activity, best captured in the high-frequency broadband (HFB; 70-170 Hz) range. On the order of hundreds of milliseconds, HFB responses peak fastest in the DAN, at intermediate speed in the SN, and slowest in the DMN. Lapses of attention (behavioral errors) are marked by distinguishable patterns of both pre- and post-stimulus HFB activity within each network. Moreover, the magnitude of temporally lagged, negative HFB coupling between the DAN and DMN (but not SN and DMN) is associated with greater sustained attention performance and is reduced during wakeful rest. These findings underscore the behavioral relevance of temporally delayed coordination between antagonistic brain networks.


Assuntos
Atenção/fisiologia , Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Fenômenos Eletrofisiológicos , Vias Neurais/fisiologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Neurociência Cognitiva , Eletrocorticografia , Humanos , Imageamento Tridimensional , Imagem por Ressonância Magnética , Rede Nervosa/fisiologia , Ondas de Rádio , Descanso , Análise e Desempenho de Tarefas
15.
Nat Neurosci ; 23(3): 433-442, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31959937

RESUMO

Neuronal computations underlying higher brain functions depend on synaptic interactions among specific neurons. A mechanistic understanding of such computations requires wiring diagrams of neuronal networks. In this study, we examined how the olfactory bulb (OB) performs 'whitening', a fundamental computation that decorrelates activity patterns and supports their classification by memory networks. We measured odor-evoked activity in the OB of a zebrafish larva and subsequently reconstructed the complete wiring diagram by volumetric electron microscopy. The resulting functional connectome revealed an over-representation of multisynaptic connectivity motifs that mediate reciprocal inhibition between neurons with similar tuning. This connectivity suppressed redundant responses and was necessary and sufficient to reproduce whitening in simulations. Whitening of odor representations is therefore mediated by higher-order structure in the wiring diagram that is adapted to natural input patterns.


Assuntos
Odorantes , Bulbo Olfatório/fisiologia , Algoritmos , Animais , Conectoma , Fenômenos Eletrofisiológicos/fisiologia , Larva , Memória/fisiologia , Modelos Neurológicos , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Condutos Olfatórios/fisiologia , Percepção Olfatória , Sinapses/fisiologia , Peixe-Zebra
16.
PLoS One ; 15(1): e0228076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978197

RESUMO

Electrical recording permits direct readout of neural activity but offers limited ability to correlate it to the network topography. On the other hand, optical imaging reveals the architecture of neural circuits, but relies on bulky optics and fluorescent reporters whose signals are attenuated by the brain tissue. Here we introduce implantable devices to record brain activities based on the field effect, which can be further extended with capability of label-free electrophysiological mapping. Such devices reply on light-addressable potentiometric sensors (LAPS) coupled to polymer fibers with integrated electrodes and optical waveguide bundles. The LAPS utilizes the field effect to convert electrophysiological activity into regional carrier redistribution, and the neural activity is read out in a spatially resolved manner as a photocurrent induced by a modulated light beam. Spatially resolved photocurrent recordings were achieved by illuminating different pixels within the fiber bundles. These devices were applied to record local field potentials in the mouse hippocampus. In conjunction with the raster-scanning via the single modulated beam, this technology may enable fast label-free imaging of neural activity in deep brain regions.


Assuntos
Encéfalo/fisiologia , Polímeros/química , Animais , Eletrodos , Fenômenos Eletrofisiológicos , Concentração de Íons de Hidrogênio , Luz , Masculino , Camundongos Endogâmicos C57BL , Cimento de Policarboxilato/química , Polimetil Metacrilato/química , Temperatura
17.
PLoS Biol ; 18(1): e3000570, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31971946

RESUMO

Stimuli that modulate neuronal activity are not always detectable, indicating a loss of information between the modulated neurons and perception. To identify where in the macaque visual system information about periodic light modulations is lost, signal-to-noise ratios were compared across simulated cone photoreceptors, lateral geniculate nucleus (LGN) neurons, and perceptual judgements. Stimuli were drifting, threshold-contrast Gabor patterns on a photopic background. The sensitivity of LGN neurons, extrapolated to populations, was similar to the monkeys' at low temporal frequencies. At high temporal frequencies, LGN sensitivity exceeded the monkeys' and approached the upper bound set by cone photocurrents. These results confirm a loss of high-frequency information downstream of the LGN. However, this loss accounted for only about 5% of the total. Phototransduction accounted for essentially all of the rest. Together, these results show that low temporal frequency information is lost primarily between the cones and the LGN, whereas high-frequency information is lost primarily within the cones, with a small additional loss downstream of the LGN.


Assuntos
Macaca fascicularis/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Percepção Visual/fisiologia , Animais , Núcleo de Edinger-Westphal/citologia , Núcleo de Edinger-Westphal/fisiologia , Núcleo de Edinger-Westphal/efeitos da radiação , Fenômenos Eletrofisiológicos , Corpos Geniculados/citologia , Corpos Geniculados/fisiologia , Luz , Iluminação , Masculino , Neurônios/fisiologia , Neurônios/efeitos da radiação , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones/citologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Fotorreceptoras Retinianas Cones/efeitos da radiação , Movimentos Sacádicos/fisiologia , Fatores de Tempo , Córtex Visual/efeitos da radiação , Vias Visuais/efeitos da radiação , Percepção Visual/efeitos da radiação
18.
Am J Physiol Heart Circ Physiol ; 318(2): H212-H222, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834838

RESUMO

The cardiac potassium IKs current is carried by a channel complex formed from α-subunits encoded by KCNQ1 and ß-subunits encoded by KCNE1. Deleterious mutations in either gene are associated with hereditary long QT syndrome. Interactions between the transmembrane domains of the α- and ß-subunits determine the activation kinetics of IKs. A physical and functional interaction between COOH termini of the proteins has also been identified that impacts deactivation rate and voltage dependence of activation. We sought to explore the specific physical interactions between the COOH termini of the subunits that confer such control. Hydrogen/deuterium exchange coupled to mass spectrometry narrowed down the region of interaction to KCNQ1 residues 352-374 and KCNE1 residues 70-81, and provided evidence of secondary structure within these segments. Key mutations of residues in these regions tended to shift voltage dependence of activation toward more depolarizing voltages. Double-mutant cycle analysis then revealed energetic coupling between KCNQ1-I368 and KCNE1-D76 during channel activation. Our results suggest that the proximal COOH-terminal regions of KCNQ1 and KCNE1 participate in a physical and functional interaction during channel opening that is sensitive to perturbation and may explain the clustering of long QT mutations in the region.NEW & NOTEWORTHY Interacting ion channel subunits KCNQ1 and KCNE1 have received intense investigation due to their critical importance to human cardiovascular health. This work uses physical (hydrogen/deuterium exchange with mass spectrometry) and functional (double-mutant cycle analyses) studies to elucidate precise and important areas of interaction between the two proteins in an area that has eluded structural definition of the complex. It highlights the importance of pathogenic mutations in these regions.


Assuntos
Citoplasma/metabolismo , Canal de Potássio KCNQ1/química , Canal de Potássio KCNQ1/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/química , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Animais , Clonagem Molecular , Cricetinae , Deutério/metabolismo , Fenômenos Eletrofisiológicos , Células HEK293 , Humanos , Hidrogênio/metabolismo , Canal de Potássio KCNQ1/genética , Síndrome do QT Longo/genética , Síndrome do QT Longo/metabolismo , Mutação , Plasmídeos/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética
19.
Bioelectrochemistry ; 132: 107410, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31821903

RESUMO

Robust control of anterior-posterior axial patterning during regeneration is mediated by bioelectric signaling. However, a number of systems-level properties of bioelectrochemical circuits, including stochastic outcomes such as seen in permanently de-stabilized "cryptic" flatworms, are not completely understood. We present a bioelectrical model for head-tail patterning that combines single-cell characteristics such as membrane ion channels with multicellular community effects via voltage-gated gap junctions. It complements the biochemically-focused models by describing the effects of intercellular electrochemical coupling, cutting plane, and gap junction blocking of the multicellular ensemble. We provide qualitative insights into recent experiments concerning planarian anterior/posterior polarity by showing that: (i) bioelectrical signals can help separated cell domains to know their relative position after injury and contribute to the transitions between the abnormal double-head state and the normal head-tail state; (ii) the bioelectrical phase-space of the system shows a bi-stability region that can be interpreted as the cryptic system state; and (iii) context-dependent responses are obtained depending on the cutting plane position, the initial bioelectrical state of the multicellular system, and the intercellular connectivity. The model reveals how simple bioelectric circuits can exhibit complex tissue-level patterning and suggests strategies for regenerative control in vivo and in synthetic biology contexts.


Assuntos
Padronização Corporal , Junções Comunicantes/metabolismo , Canais Iônicos/metabolismo , Animais , Fenômenos Eletrofisiológicos , Cabeça/fisiologia , Planárias/metabolismo , Planárias/fisiologia , Cauda/fisiologia
20.
Muscle Nerve ; 61(2): 131-142, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31579956

RESUMO

Electromyography (EMG) assesses the anatomic motor unit (A-MU), but knowledge of its anatomy, physiology, and changes with pathology is limited. The electrophysiological motor unit (E-MU) and its motor unit potential (E-MUP) represents a fraction of the A-MU. Routine EMG assesses a limited number of E-MUP waveform characteristics (metrics) and their magnitudes qualitatively scaled in a nonlinear manner. Another approach is quantitative EMG (QEMG), whereby 20+ E-MUPs are extracted and both basic and derived metrics obtained and values expressed quantitatively. In diseased muscle, many E-MUP metrics may be normal, which complicates diagnostic interpretation. In QEMG, E-MUP metrics can be clustered and statistical analyses performed to assign probabilities that E-MUPs (and the muscle) are normal, neuropathic, or myopathic. In this article we review what is known about the A-MU, the restricted E-MU, E-MUP metrics, and what QEMG offers currently and in the future.


Assuntos
Eletromiografia/métodos , Neurônios Motores/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Potenciais de Ação/fisiologia , Animais , Fenômenos Eletrofisiológicos , Potenciais Evocados/fisiologia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA