Synthesis, screening for antiacetylcholinesterase activity and binding mode prediction of a new series of [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters

A series of nine new [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters (phosphate-carbamate compounds) was obtained through the reaction of (4,4,4-trifluoro-3-hydroxybut-1-yl)-carbamic acid ethyl esters with phosphorus oxychloride followed by the addition of alcohols. The products were characterized by ¹H, 13C, 31P, and 19F NMR spectroscopy, GC-MS, and elemental analysis. All the synthesized compounds were screened for acetylcholinesterase (AChE) inhibitory activity using the Ellman method. All compounds containing phosphate and carbamate pharmacophores in their structures showed enzyme inhibition, being the compound bearing the diethoxy phosphate group (2b) the most active compound. Molecular modeling studies were performed to investigate the detailed interactions between AChE active site and small-molecule inhibitor candidates, providing valuable structural insights into AChE inhibition.

Marine influence in the Barreiras Formation, State of Alagoas, northeastern Brazil

Tidal processes were important for deposition of the Barreiras Formation located in northern Brazil, while correlatable deposits in northeastern Brazil have been traditionally related to continental environments. Facies analysis in southern Alagoas revealed that the Barreiras Formation consists of cross-stratified conglomerates and sandstones (facies Sx and Cgx), compound cross-stratified sandstones (facies Cx), and heterolithic beddings (facies H). A significant portion of these deposits occurs within channel morphologies displaying fining and thinning upward successions. An abundance of sedimentary features is comparable to those from the northern Brazilian counterpart. These include: tidal bundles; herringbone cross-stratification; heterolithic beddings with sandstone and mudstone beds in sharp contacts; and ichnofossils mostly consisting of Ophiomorpha nodosa, Skolithos and Planolites. Altogether, these features point to a marginal marine depositional setting dominated by tidal processes, which are related to an estuarine system, an interpretation also provided for the Barreiras Formation in northern Brazil. The widespread occurrence of deposits with unambiguous evidence of tidal processes in the Barreiras Formation of northern Brazil, and now in the State of Alagoas, leads to argue that the early/middle Miocene worldwide marine transgression might have left a much more widespread sedimentary record along the Brazilian coast than currently regarded.

A novel polar-based human face recognition computational model

Motivated by a recently proposed biologically inspired face recognition approach, we investigated the relation between human behavior and a computational model based on Fourier-Bessel (FB) spatial patterns. We measured human recognition performance of FB filtered face images using an 8-alternative forced-choice method. Test stimuli were generated by converting the images from the spatial to the FB domain, filtering the resulting coefficients with a band-pass filter, and finally taking the inverse FB transformation of the filtered coefficients. The performance of the computational models was tested using a simulation of the psychophysical experiment. In the FB model, face images were first filtered by simulated V1- type neurons and later analyzed globally for their content of FB components. In general, there was a higher human contrast sensitivity to radially than to angularly filtered images, but both functions peaked at the 11.3-16 frequency interval. The FB-based model presented similar behavior with regard to peak position and relative sensitivity, but had a wider frequency band width and a narrower response range. The response pattern of two alternative models, based on local FB analysis and on raw luminance, strongly diverged from the human behavior patterns. These results suggest that human performance can be constrained by the type of information conveyed by polar patterns, and consequently that humans might use FB-like spatial patterns in face processing.

Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats

Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

Identificação de operantes verbais constituintes da leitura por meio da análise dos movimentos dos olhos

Os movimentos dos olhos produzem estímulos discriminativos para o comportamento de ler. O presente estudo teve por objetivo analisar os movimentos dos olhos de dois participantes durante a leitura de anagramas e identificar os operantes verbais envolvidos. A tarefa consistia em vocalizar uma palavra utilizando cinco letras. Na Fase 1, as letras formavam apenas uma palavra, sempre que observadas em uma mesma sequência espacial. Na Fase 2, formavam duas ou mais a partir de diferentes sequências. Na Fase 2, apesar da possibilidade de múltipla formação de palavras, as palavras vocalizadas foram aquelas formadas pela mesma sequência reforçada na fase anterior. Com base nos movimentos dos olhos, as vocalizações foram analisadas à luz dos conceitos de comportamento textual, auto-correção e intraverbal.

Estímulo discriminativo de extinção produzido por respostas de observação em pombos

Pombos privados de comida foram expostos a tentativas que podiam terminar com ou sem a apresentação de comida independentemente de qualquer resposta. Durante uma tentativa, bicadas podiam mudar a cor do disco de resposta de branco para verde (S+) ou vermelho (S-) a depender do acionamento (ou não) do comedouro. Em linha de base, bicadas produziam ambas as cores em intervalos médios variáveis de 15 s. Em duas condições experimentais distintas, tandem VI DRH foi empregado na produção, ora de S+, ora de S-. Resultados mostraram que o esquema tandem levou a uma diminuição geral na freqüência de estímulos discriminativos produzidos, marcadamente na de S+, mas não na de S-. Esses dados fornecem suporte para o modelo de reforçamento condicionado baseado na redução da incerteza.

Análises do matching de identidade generalizado por contingências de três e quatro termos: implicações para equivalência de estímulos

A expansão da tríplice continência em unidades com quatro ou mais elementos abriu novas perspectivas para a compreensão de comportamentos complexos, como a emergência de respostas que derivam da formação de classes de estímulos equivalentes e que modelam comportamentos simbólicos e conceituais. Na investigação experimental, o procedimento de matching to sample tem sido frequentemente empregado para estabelecer discriminações condicionais. Em particular, a obtenção do matching de identidade generalizado é considerada demonstrativa da aquisição dos conceitos de igualdade e diferença. Segundo argumentamos, o fato de se buscar a compreensão desses conceitos a partir de processos discriminativos condicionais pode ter sido responsável pelos frequentes fracassos em demonstrá-los em sujeitos não humanos. A falta de correspondência entre os processos discriminativos responsáveis por estabelecer a relação de reflexividade entre estímulos que formam classes equivalentes e o matching de identidade generalizado, nesse sentido, é aqui revista ao longo de estudos empíricos e discutida com respeito às suas implicações.

Efeitos da exposição a estímulos aversivos e apetitivos incontroláveis sobre o comportamento verbal em contingências de reforço positivo

Foram analisados efeitos de diferentes histórias de incontrolabilidade por perda ou ganho de pontos sobre o desempenho posterior de participantes humanos na construção de frases. Inicialmente, os participantes podiam ganhar ou perder pontos independentemente de qualquer característica da frase construída. Posteriormente, recebiam pontos por construir frases iniciadas apenas pelo pronome "ele". Os resultados mostram que a exposição à incontrolabilidade pode dificultar condições posteriores de novas aprendizagens sob reforçamento positivo. Interessantemente, essas dificuldades foram menos acentuadas e, em certos casos, até mesmo superadas, no caso de uma história de exposição a ganhos incontroláveis de pontos. Em contrapartida, no caso de uma história de perdas incontroláveis de pontos, aprendizagens subsequentes sob reforço positivo tenderam a ser prejudicadas. Esses resultados contribuem para os estudos de incontrolabilidade e desamparo aprendido, em particular por apresentar alternativas metodológicas passíveis de aplicação a respostas verbais em humanos.

Psychophysical measurements of luminance and chromatic spatial and temporal contrast sensitivity in Duchenne muscular dystrophy

In children with Duchenne muscular dystrophy, color vision losses have been related to dystrophin deletions downstream of exon 30, which affect a dystrophin isoform, Dp260, present in the retina. To further evaluate visual function in DMD children, we measured spatial, temporal, and chromatic red-green and blue-yellow contrast sensitivity in two groups of DMD children with gene deletion downstream and upstream of exon 30. Psychophysical spatial contrast sensitivity was measured for low, middle, and high spatial frequencies with achromatic gratings and for low and middle frequencies with red-green and blue-yellow chromatic gratings. Temporal contrast sensitivity was also measured with achromatic stimuli. A reduction in sensitivity at all spatial luminance contrasts was found for the DMD patients with deletion downstream of exon 30. Similar results were found for temporal luminance contrast sensitivity. Red-green chromatic contrast sensitivity was reduced in DMD children with deletion downstream of exon 30, whereas blue-yellow chromatic contrast sensitivity showed no significant differences. We conclude that visual function is impaired in DMD children. Furthermore, we report a genotype-phenotype relationship because the visual impairment occurred in children with deletion downstream but not upstream of exon 30, affecting the retinal isoform of dystrophin Dp260.

Learning processes and the neural analysis of conditioning

Classical and operant conditioning principles, such as the behavioral discrepancy-derived assumption that reinforcement always selects antecedent stimulus and response relations, have been studied at the neural level, mainly by observing the strengthening of neuronal responses or synaptic connections. A review of the literature on the neural basis of behavior provided extensive scientific data that indicate a synthesis between the two conditioning processes based mainly on stimulus control in learning tasks. The resulting analysis revealed the following aspects. Dopamine acts as a behavioral discrepancy signal in the midbrain pathway of positive reinforcement, leading toward the nucleus accumbens. Dopamine modulates both types of conditioning in the Aplysia mollusk and in mammals. In vivo and in vitro mollusk preparations show convergence of both types of conditioning in the same motor neuron. Frontal cortical neurons are involved in behavioral discrimination in reversal and extinction procedures, and these neurons preferentially deliver glutamate through conditioned stimulus or discriminative stimulus pathways. Discriminative neural responses can reliably precede operant movements and can also be common to stimuli that share complex symbolic relations. The present article discusses convergent and divergent points between conditioning paradigms at the neural level of analysis to advance our knowledge on reinforcement.

Detecção de estímulos concêntricos mesópicos em crianças surdas e ouvintes

O objetivo deste trabalho foi medir curvas de sensibilidade ao contraste de 10 crianças ouvintes e de 10 crianças com surdez pré-lingual, de 7 a 12 anos, utilizando frequências radiais circularmente concêntricas (FSCr) de 0,25-2,0 cpg em níveis baixos de luminância (0,7 cd/m²). Todos os participantes apresentavam acuidade visual normal e estavam livres de doenças oculares identificáveis. A FSCr foi medida com o método psicofísico da escolha forçada. Os resultados mostraram sensibilidade máxima na faixa de frequência radial de 0,25 cpg para os dois grupos. Os resultados mostraram ainda diferenças significantes entre as curvas de FSCr de crianças ouvintes e de crianças com surdez pré-lingual. Isto é, as crianças ouvintes precisaram de menos contraste do que as crianças surdas para detectar as frequências radiais. Esses resultados sugerem que, em níveis baixos de luminância, a FSCr das crianças ouvintes foi melhor do que a das crianças com surdez pré-lingual.

Visual contrast sensitivity in tonic-clonic epileptic patients

We measured the effects of epilepsy on visual contrast sensitivity to linear and vertical sine-wave gratings. Sixteen female adults, aged 21 to 50 years, comprised the sample in this study, including eight adults with generalized tonic-clonic seizure-type epilepsy and eight age-matched controls without epilepsy. Contrast threshold was measured using a temporal two-alternative forced-choice binocular psychophysical method at a distance of 150 cm from the stimuli, with a mean luminance of 40.1 cd/m². A one-way analysis of variance (ANOVA) applied to the linear contrast threshold showed significant differences between groups (F[3,188] = 14.829; p < .05). Adults with epilepsy had higher contrast thresholds (1.45, 1.04, and 1.18 times for frequencies of 0.25, 2.0, and 8.0 cycles per degree of visual angle, respectively). The Tukey Honestly Significant Difference post hoc test showed significant differences (p < .05) for all of the tested spatial frequencies. The largest difference between groups was in the lowest spatial frequency. Therefore, epilepsy may cause more damage to the neural pathways that process low spatial frequencies. However, epilepsy probably alters both the magnocellular visual pathway, which processes low spatial frequencies, and the parvocellular visual pathway, which processes high spatial frequencies. The experimental group had lower visual contrast sensitivity to all tested spatial frequencies.

Caracterização mecânica e térmica da borracha natural formulada e vulcanizada dos clones: GT 1, IAN 873, PB 235 e RRIM 600

Neste trabalho estudou-se o desempenho mecânico e térmico de compostos de borracha natural (Hevea brasiliensis) de 4 diferentes clones (GT 1, IAN 873, PB 235 e RRIM 600) cultivados no Estado de São Paulo, assim como de uma mistura destes clones e de uma borracha comercial, GEB-1. Estas borrachas foram formuladas e vulcanizadas com tempos de 5, 7 e 9 minutos. A caracterização foi realizada por calorimetria exploratória diferencial, termogravimetria, ensaios de resistência à tração, análise dinâmico-mecânica, medidas de dureza Shore A, microscopia eletrônica de varredura e espectroscopia na região do infravermelho. Os resultados permitiram concluir que o tempo de vulcanização e o tipo de clone não influenciaram na temperatura de transição vítrea (Tg) dos compostos. Os valores de Tg obtidos por DMA foram de cerca de -62 °C, e os resultados ensaios de dureza apresentaram valores próximos de 60 para todos os compostos estudados. Os ensaios de resistência à tração mostraram que o melhor desempenho mecânico foi obtido pelo clone RRIM 600. De acordo com os resultados obtidos neste trabalho, todos os clones atingiram as propriedades reportadas na literatura, podendo ser utilizados, em princípio, nas indústrias de artefatos de borracha separadamente ou na forma de mistura.

HPLC microfractionation of flavones and antioxidant (radical scavenging) activity of Saccharum officinarum L.

The antioxidant activity of sugarcane (Saccharum officinarum L.) juice towards DPPH reagent was determined (EC50) and the main compounds with radical scavenging activity in juice and leaves extracts were identified by HPLC-UV/PAD analysis combined with HPLC microfractionation monitored by TLC using β-carotene and DPPH as the detection reagents. In sugarcane leaves, luteolin-8-C-(rhamnosylglucoside) (1) was the most important compound with radical scavenging activity; in sugarcane juice, the flavones diosmetin-8-C-glucoside (2), vitexin (3) schaftoside (9), isoschaftoside (10) and 4',5'-dimethyl-luteolin-8-C-glucoside (11) were the most relevant compounds. The content of juice flavonoids (0.241 ± 0.001 mg total flavonoids/mL juice), comparable to other food sources of flavonoids, suggest the potential of sugarcane as a dietary source of natural antioxidants. However, the low antioxidant ability of sugarcane juice (EC50 = 100.2 ± 2.6 g L-1) also points to the need for further studies about the dietary intake of sugarcane flavonoids and its effects on human health.

Characterization studies of 1-(4-cyano-2-oxo-1,2-dihydro-1-pyridyl)-3-(4-cyano-1,2-dihydro-1-pyridyl)propane formed from the reaction of hydroxide Ion with 1,3-Bis-(4-cyano pyridinium)propane

The aqueous alkaline reaction of 1,3-bis(4-cyanopyridinium)propane dibromide, a reactant constituted of two pyridinium rings linked by a three-methylene bridge, generates a novel compound,1 -(4-cyano-2-oxo-1,2-dihydro-1-pyridyl)-3-(4-cyano-1,2-dihydro-1-pyridyl)propane. The reaction pathway is attributed to the proximity of the OH- ion inserted between two pyridinium moieties, which occurs only in bis(pyridinium) derivatives connected by short methylene spacers, where charge-conformational effects are important.