Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation.

A critical issue in brain energy metabolism is whether lactate produced within the brain by astrocytes is taken up and metabolized by neurons upon activation. Although there is ample evidence that neurons can efficiently use lactate as an energy substrate, at least in vitro, few experimental data exist to indicate that it is indeed the case in vivo. To address this question, we used a modeling approach to determine which mechanisms are necessary to explain typical brain lactate kinetics observed upon activation. On the basis of a previously validated model that takes into account the compartmentalization of energy metabolism, we developed a mathematical model of brain lactate kinetics, which was applied to published data describing the changes in extracellular lactate levels upon activation. Results show that the initial dip in the extracellular lactate concentration observed at the onset of stimulation can only be satisfactorily explained by a rapid uptake within an intraparenchymal cellular compartment. In contrast, neither blood flow increase, nor extracellular pH variation can be major causes of the lactate initial dip, whereas tissue lactate diffusion only tends to reduce its amplitude. The kinetic properties of monocarboxylate transporter isoforms strongly suggest that neurons represent the most likely compartment for activation-induced lactate uptake and that neuronal lactate utilization occurring early after activation onset is responsible for the initial dip in brain lactate levels observed in both animals and humans.

Measuring brain perfusion with intravoxel incoherent motion (IVIM): Initial clinical experience.

PURPOSE: To evaluate the feasibility of intravoxel incoherent motion (IVIM) perfusion measurements in the brain with currently available imaging systems. MATERIALS AND METHODS: We acquired high in-plane resolution (1.2 × 1.2 mm(2) ) diffusion-weighted images with 16 different values of b ranging from 0 to 900 s/mm(2) , in three orthogonal directions, on 3T systems with a 32-multichannel receiver head coil. IVIM perfusion maps were extracted by fitting a double exponential model of signal amplitude decay. Regions of interest were drawn in pathological and control regions, where IVIM perfusion parameters were compared to the corresponding dynamic susceptibility contrast (DSC) parameters. RESULTS: Hyperperfusion was found in the nonnecrotic or cystic part of two histologically proven glioblastoma multiforme and in two histologically proven glioma WHO grade III, as well as in a brain metastasis of lung adenocarcinoma, in a large meningioma, and in a case of ictal hyperperfusion. A monoexponential decay was found in a territory of acute ischemia, as well as in the necrotic part of a glioblastoma. The IVIM perfusion fraction f correlated well with DSC CBV. CONCLUSION: Our initial report suggests that high-resolution brain perfusion imaging is feasible with IVIM in the current clinical setting. J. Magn. Reson. Imaging 2014;39:624-632. © 2013 Wiley Periodicals, Inc.

Estimation of the noisy component of anatomical backgrounds.

The knowledge of the relationship that links radiation dose and image quality is a prerequisite to any optimization of medical diagnostic radiology. Image quality depends, on the one hand, on the physical parameters such as contrast, resolution, and noise, and on the other hand, on characteristics of the observer that assesses the image. While the role of contrast and resolution is precisely defined and recognized, the influence of image noise is not yet fully understood. Its measurement is often based on imaging uniform test objects, even though real images contain anatomical backgrounds whose statistical nature is much different from test objects used to assess system noise. The goal of this study was to demonstrate the importance of variations in background anatomy by quantifying its effect on a series of detection tasks. Several types of mammographic backgrounds and signals were examined by psychophysical experiments in a two-alternative forced-choice detection task. According to hypotheses concerning the strategy used by the human observers, their signal to noise ratio was determined. This variable was also computed for a mathematical model based on the statistical decision theory. By comparing theoretical model and experimental results, the way that anatomical structure is perceived has been analyzed. Experiments showed that the observer's behavior was highly dependent upon both system noise and the anatomical background. The anatomy partly acts as a signal recognizable as such and partly as a pure noise that disturbs the detection process. This dual nature of the anatomy is quantified. It is shown that its effect varies according to its amplitude and the profile of the object being detected. The importance of the noisy part of the anatomy is, in some situations, much greater than the system noise. Hence, reducing the system noise by increasing the dose will not improve task performance. This observation indicates that the tradeoff between dose and image quality might be optimized by accepting a higher system noise. This could lead to a better resolution, more contrast, or less dose.

Estimativa do número apropriado de progênies S1 para a seleção recorrente em milho

O objetivo deste trabalho foi determinar o número desejável de progênies S1 para avaliação em programas de seleção recorrente em milho (Zea mays L.). Foram avaliadas, em blocos casualizados, em dois locais e três repetições por local, 200 progênies das populações BR-105 e BR-106. As 200 progênies de cada população foram divididas ao acaso em grupos de 25, sendo que os tamanhos amostrais foram de 25 até 200 progênies. Em cada amostra, as variâncias genética e fenotípica, o coeficiente de herdabilidade e os respectivos intervalos de confiança foram estimados quanto aos caracteres peso de espigas (PE), altura da planta (AP), altura da espiga (AE) e prolificidade (PR). Verificou-se que com o aumento do número de progênies avaliadas, a amplitude dos intervalos de confiança dos parâmetros estimados decresceram, em relação aos caracteres avaliados em ambas as populações. As estimativas dos parâmetros e os intervalos de confiança da análise de peso de espiga, estabilizaram-se ao redor de 175-200 progênies, em ambas as populações. Quanto a AP, AE e PR, os parâmetros estimados se estabilizaram em torno de 125, 125 e 175 progênies, respectivamente, em ambas as populações. Assim, conclui-se que em programas de seleção recorrente, no mínimo 200 progênies poderiam ser usadas, independentemente do tipo de população.

Intervalo de confiança "bootstrap" como ferramenta para classificar raças do nematóide de cisto da soja

Estimativas "bootstrap" da média aritmética dos genótipos de soja 'Pickett', 'Peking', PI88788 e PI90763 e os intervalos de confiança obtidos pela teoria normal e através da distribuição "bootstrap" deste estimador, como o percentil "bootstrap" e o BCa, correção para o viés e aceleração, do parâmetro de diferenciação da cultivar padrão de suscetibilidade Lee são utilizados para classificar raças do nematóide de cisto da soja. Os intervalos de confiança obtidos a partir da distribuição "bootstrap" apresentaram menor amplitude e foram muito similares, dessa forma, o limite inferior do intervalo de confiança percentil "bootstrap" foi tomado como nível de referência nas distribuições "bootstrap" do estimador da média aritmética dos genótipos diferenciadores, permitindo estimar a probabilidade empírica de uma reação positiva ou negativa, e, conseqüentemente, identificar a raça mais provável sob determinado teste.

Análise de covariância para melhoria da capacidade de discriminação em ensaios de cultivares de milho

O uso de técnicas experimentais visando à precisão em detectar diferenças no rendimento de grãos é muito importante. O objetivo deste trabalho foi verificar a viabilidade da análise da covariância, como forma de reduzir o erro experimental. Foram utilizados os dados de rendimento de grãos de milho (Zea mays L.) e da população final de plantas das unidades experimentais de 313 ensaios de competição de cultivares, conduzidos no Estado do Rio Grande do Sul nos anos de 1993/96. Para fins de comparação entre a precisão da análise com e sem o uso da covariância, criou-se uma estatística denominada HD, que é igual à amplitude entre as médias estimadas das cultivares, dividida pelo valor da diferença mínima significativa (DMS) do teste de Tukey. Quanto maior for o valor de HD, melhor será a qualidade do ensaio, por permitir melhor discriminação entre as cultivares. O uso da análise da covariância elevou a estatística HD de 4,7 para 19,5, e melhorou a discriminação entre as médias ajustadas pela covariável população final de plantas.

Effect of abscisic acid on maize root gravireaction

Primary roots of intact maize seedlings (cv. LG11) were pretreated when kept vertically (1 or 2 in the dark) with a droplet of buffer solution containing ABA (at different concentrations) applied to the root tip. Then, apical root segments were prepared and placed horizontally in both light and darkness. The downward curvature was measured. In the light, curvature was greater than in darkness and ABA (5×10−5 mol·dm−3) significantly enhanced the curvature in both darkness and light. The amplitude of the increase in the gravireaction was found to be dependent on the ABA concentration and the duration of the pretreatment.

Kinetics of atrial repolarization alternans in a free-behaving ovine model.

Kinetics of Atrial Repolarization Alternans. INTRODUCTION: Repolarization alternans (Re-ALT), a beat-to-beat alternation in action potential repolarization, promotes dispersion of repolarization, wavebreaks, and reentry. Recently, Re-ALT has been shown to play an important role in the transition from rapid pacing to atrial fibrillation (AF) in humans. The detailed kinetics of atrial Re-ALT, however, has not been reported so far. We developed a chronic free-behaving ovine pacing model to study the kinetics of atrial Re-ALT as a function of pacing rate. METHODS: Thirteen sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms and delivery of rapid pacing protocols. Beat-to-beat differences in the atrial T-wave apex amplitude as a measure of Re-ALT and activation time were analyzed at incremental pacing rates until the effective refractory period (ERP) defined as stable 2:1 capture. RESULTS: Atrial Re-ALT appeared intermittently but without periodicity, and increased in amplitude as a function of pacing rate until ERP. Intermittent 2:1 atrial capture was observed at pacing cycle lengths 40 ms above ERP, and increased in duration as a function of pacing rate. Episodes of rapid pacing-induced AF were rare, and were preceded by Re-ALT or complex oscillations of atrial repolarization, but without intermittent capture. CONCLUSION: We show in vivo that atrial Re-ALT developed and increased in magnitude with rate until stable 2:1 capture. In rare instances where capture failure did not occur, Re-ALT and complex oscillations of repolarization surged and preceded AF initiation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1003-1012, September 2012).

Efeito de época de semeadura e adubação na mancha-foliar de Phaeosphaeria em milho

O aumento da área de cultivo de milho, aliado a algumas práticas culturais, tem favorecido o surgimento da mancha-foliar causada pelo fungo Phaeosphaeria maydis. Como conseqüência, o rendimento de grãos tem decrescido, especialmente em áreas com plantio direto e maior amplitude da época de semeadura. O trabalho teve como objetivo avaliar a severidade de P. maydis em seis híbridos de milho, em cinco épocas de semeadura e em dois níveis de adubação. O experimento foi conduzido em Xanxerê, SC, na safra 1997/98, em blocos casualizados, com parcelas subdivididas, em duas repetições. As plantas foram avaliadas 30 dias após o florescimento, e a porcentagem da área foliar afetada foi registrada. Na medida em que a semeadura do milho foi retardada, houve um aumento na severidade da moléstia e uma redução no rendimento de grãos. As doses de adubação não apresentaram diferença quanto à severidade da moléstia. O mês de setembro apresentou menor severidade da mancha-foliar e maior rendimento de grãos. Houve uma correlação significativa entre o rendimento de grãos e a severidade da moléstia.

Age-related differences on event-related potentials and brain rhythm oscillations during working memory activation.

Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive-negative working memory (PN(wm)) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN(wm) component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN(wm) area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.

Clinical and electrophysiological recovery in Leber hereditary optic neuropathy with G3460A mutation.

To report a case of clinical and electrophysiological recovery in Leber hereditary optic neuropathy (LHON) with G3460A Mutation. A 10-year-old boy with a three-month history of painless bilateral sequential visual loss upon presentation underwent visual acuity (diminished), anterior and posterior segment examination (normal), fluorescein angiography (normal), Goldman kinetic perimetry (bilateral central scotomata), genetic (a point G3460A mutation) and electrophysiological investigation (undetectable pattern visual evoked potentials (VEP); low amplitude, broadened and reduced flash VEPs and loss of the N95 component in the pattern electroretinograms). Diagnosis of LHON was made. Eighteen months later vision and electrophysiological tests results began spontaneously improving. Kinetic perimetry revealed reduced density and size of scotomata. Two years later, there had been further electrophysiological improvement. This report describes both clinical and electrophysiological improvement in LHON with G3460A mutation.

Herança da resistência à mancha-foliar de feosféria em milho

A mancha-foliar de feosféria tem causado expressiva redução no rendimento de grãos de milho, no Brasil, principalmente, em decorrência da crescente amplitude da data de semeadura, conjugada com o uso de áreas irrigadas e de plantio direto. É importante o desenvolvimento de genótipos resistentes a essa moléstia; porém a realização de uma seleção eficiente depende do entendimento da variabilidade genética e da herança da resistência. Com o objetivo de determinar a capacidade combinatória e o modo de herança do caráter, foram cruzadas sete linhagens de milho, para a realização das análises dialélica e média de gerações. Os experimentos foram conduzidos no Município de Xanxerê, SC, sendo avaliada a porcentagem de tecido foliar afetado pela moléstia 30 dias após o florescimento. Os genótipos apresentaram amplitude de 4,3% a 67,0% de área foliar afetada pela moléstia, na qual a linhagem LA06 e seus híbridos demonstraram elevada resistência. Os resultados indicaram que a seleção de genótipos resistentes à feosféria pode ser realizada com sucesso em programas de melhoramento do milho, visto que a manifestação do caráter é controlada por, pelo menos, dois genes independentes e com uma efetiva participação de efeitos aditivos.

High precision anatomy for MEG.

Precise MEG estimates of neuronal current flow are undermined by uncertain knowledge of the head location with respect to the MEG sensors. This is either due to head movements within the scanning session or systematic errors in co-registration to anatomy. Here we show how such errors can be minimized using subject-specific head-casts produced using 3D printing technology. The casts fit the scalp of the subject internally and the inside of the MEG dewar externally, reducing within session and between session head movements. Systematic errors in matching to MRI coordinate system are also reduced through the use of MRI-visible fiducial markers placed on the same cast. Bootstrap estimates of absolute co-registration error were of the order of 1mm. Estimates of relative co-registration error were <1.5mm between sessions. We corroborated these scalp based estimates by looking at the MEG data recorded over a 6month period. We found that the between session sensor variability of the subject's evoked response was of the order of the within session noise, showing no appreciable noise due to between-session movement. Simulations suggest that the between-session sensor level amplitude SNR improved by a factor of 5 over conventional strategies. We show that at this level of coregistration accuracy there is strong evidence for anatomical models based on the individual rather than canonical anatomy; but that this advantage disappears for errors of greater than 5mm. This work paves the way for source reconstruction methods which can exploit very high SNR signals and accurate anatomical models; and also significantly increases the sensitivity of longitudinal studies with MEG.

Chronic low-frequency rTMS of primary motor cortex diminishes exercise training-induced gains in maximal voluntary force in humans.

Although there is consensus that the central nervous system mediates the increases in maximal voluntary force (maximal voluntary contraction, MVC) produced by resistance exercise, the involvement of the primary motor cortex (M1) in these processes remains controversial. We hypothesized that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of M1 during resistance training would diminish strength gains. Forty subjects were divided equally into five groups. Subjects voluntarily (Vol) abducted the first dorsal interosseus (FDI) (5 bouts x 10 repetitions, 10 sessions, 4 wk) at 70-80% MVC. Another group also exercised but in the 1-min-long interbout rest intervals they received rTMS [Vol+rTMS, 1 Hz, FDI motor area, 300 pulses/session, 120% of the resting motor threshold (rMT)]. The third group also exercised and received sham rTMS (Vol+Sham). The fourth group received only rTMS (rTMS_only). The 37.5% and 33.3% gains in MVC in Vol and Vol+Sham groups, respectively, were greater (P = 0.001) than the 18.9% gain in Vol+rTMS, 1.9% in rTMS_only, and 2.6% in unexercised control subjects who received no stimulation. Acutely, within sessions 5 and 10, single-pulse TMS revealed that motor-evoked potential size and recruitment curve slopes were reduced in Vol+rTMS and rTMS_only groups and accumulated to chronic reductions by session 10. There were no changes in rMT, maximum compound action potential amplitude (M(max)), and peripherally evoked twitch forces in the trained FDI and the untrained abductor digiti minimi. Although contributions from spinal sources cannot be excluded, the data suggest that M1 may play a role in mediating neural adaptations to strength training.

Dinâmica populacional da mariposa oriental em pomares de pessegueiro e ameixeira

O objetivo deste trabalho foi estudar a dinâmica populacional da mariposa oriental [Grapholita molesta (Busk)] em pomares de pessegueiro e ameixeira. Os adultos foram monitorados em dois pomares de pessegueiro e um de ameixeira por cinco anos. Séries temporais equivalentes de temperaturas máximas e mínimas foram correlacionadas aos dados de flutuação populacional para se aferir a correspondência entre a ocorrência da praga e as flutuações de temperatura. A análise de Fourier das séries temporais das armadilhas de coleta de mariposas revelou dinâmicas cíclicas, com período principal médio de 53,91 semanas. Um período menor médio, de 7,45 semanas, também ficou evidente e se aproxima do tempo médio de geração do inseto. A análise do espectro de potência das séries temporais, com e sem periodicidade, revelou que a dinâmica populacional de G. molesta possui um componente regular, caracterizado pelos períodos observados, e outro componente irregular, reminiscente de ruído 1/f, caracterizado pelas variações de amplitude, aparentemente irregulares, na ocorrência do inseto. A combinação desses dois componentes ocasiona um processo com domínio de baixas freqüências, próprio das dinâmicas periódicas ruidosas. Os ciclos de aparecimento da praga ocorrem em fase com os ciclos de flutuação de temperaturas máximas e mínimas.