RESUMO
In fasted and fed states, blood insulin levels are oscillatory. While this phenomenon is well studied at high glucose levels, comparatively little is known about its origin under basal conditions. We propose a possible mechanism for basal insulin oscillations based on oscillations in glycolysis, demonstrated using an established mathematical model. At high glucose, this is superseded by a calcium-dependent mechanism.
Assuntos
Ilhotas Pancreáticas , Cálcio/metabolismo , Glucose/metabolismo , Glicólise , Humanos , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismoRESUMO
Secretion of insulin from the pancreas is pulsatile, driven by intrinsic oscillations within individual islets of Langerhans. The secretions are coordinated among the many islets distributed throughout the pancreas producing a synchronized rhythm in vivo that is essential for maintaining normal glucose levels. One hypothesized mechanism for the coordination of islet activity is negative feedback, whereby sequestration of glucose in response to elevated insulin leads to a reduction in the blood glucose level that is sensed by the islet population. This global signal of glucose then coordinates the individual islets. In this study, we tested how this coordination mechanism is affected by time delays in the negative feedback, using a microfluidic system to monitor Ca2+ levels in a small population of islets and implementing glucose control through a negative feedback system. We found that islet synchronization occurs even with time delays in the feedback of up to 7 min. We also found that a second, slower closed-loop oscillation period is produced during delayed feedback in which islet oscillations are clustered into episodes. The period of this second oscillatory mode increases with the time delay and appears to be a second stable behavior that coexists with the faster synchronized oscillation. The general conclusion is that islet coordination through negative feedback is a viable means of islet coordination that is robust to delays in the timing of the feedback, and could complement other potential coordination mechanisms such as entrainment by pancreatic ganglia.NEW & NOTEWORTHY Insulin secretion from islets of Langerhans is rhythmic, and these rhythms are coordinated to produce oscillatory plasma insulin levels. Using a combination of microfluidics and computational modeling, we demonstrate that coordination can occur through negative feedback of the type provided by the liver, even if that feedback is delayed by several minutes. We also demonstrate that a second, slower, mode of oscillations can occur when feedback is delayed where faster oscillations are grouped into episodes.
Assuntos
Ilhotas Pancreáticas , Retroalimentação , Ilhotas Pancreáticas/metabolismo , Secreção de Insulina , Insulina/metabolismo , Glucose/metabolismoRESUMO
Plasma insulin measurements from mice, rats, dogs, and humans indicate that insulin levels are oscillatory, reflecting pulsatile insulin secretion from individual islets. An unanswered question, however, is how the activity of a population of islets is coordinated to yield coherent oscillations in plasma insulin. Here, using mathematical modeling, we investigate the feasibility of a potential islet synchronization mechanism, cholinergic signaling. This hypothesis is based on well-established experimental evidence demonstrating intrapancreatic parasympathetic (cholinergic) ganglia and recent in vitro evidence that a brief application of a muscarinic agonist can transiently synchronize islets. We demonstrate using mathematical modeling that periodic pulses of acetylcholine released from cholinergic neurons is indeed able to coordinate the activity of a population of simulated islets, even if only a fraction of these are innervated. The role of islet-to-islet heterogeneity is also considered. The results suggest that the existence of cholinergic input to the pancreas may serve as a regulator of endogenous insulin pulsatility in vivo.
Assuntos
Acetilcolina/metabolismo , Gânglios Parassimpáticos/fisiologia , Ilhotas Pancreáticas/fisiologia , Modelos Neurológicos , Trifosfato de Adenosina/metabolismo , Algoritmos , Animais , Cálcio/metabolismo , Carbacol/farmacologia , Membrana Celular/fisiologia , Simulação por Computador , Citosol/metabolismo , Gânglios Parassimpáticos/efeitos dos fármacos , Glucose/metabolismo , Glicólise/fisiologia , Inositol 1,4,5-Trifosfato/metabolismo , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/inervação , Camundongos , Mitocôndrias/metabolismo , Agonistas Muscarínicos/farmacologia , PeriodicidadeRESUMO
The purpose of the present study was to compare muscular strength of knee extensors and arm flexor muscles of cardiac patients (n = 638) and healthy controls (n = 961) in different age groups. Isometric torques were measured in a sitting position with the elbow, hip, and knee flexed to 90(0). For statistical analysis, age groups were pooled in decades from the age of 30 to 90 years. Additionally, the influence of physical lifestyle prior to disease on muscular strength was obtained in the patients. For statistical analysis three-way ANOVA (factors age, gender, and physical activity level) was used.Both in patients and in controls a significant age-dependent decline in maximal torque could be observed for arm flexors and knee extensors. Maximal leg extensor muscle showed statistically significant differences between healthy controls and cardiac patients as well as between subgroups of patients: Physically inactive patients showed lowest torques (male: 148 +/- 18 Nm; female: 82 +/- 25 Nm) while highest values were measured in control subjects (male: 167 +/- 16 Nm; female: 93 +/- 17 Nm). In contrast, arm flexor muscles did not show any significant influence of health status or sports history.This qualitative difference between weight-bearing leg muscles and the muscle group of the upper extremity suggest that lower skeletal muscle strength in heart patients is mainly a consequence of selective disuse of leg muscles rather than any pathological skeletal muscle metabolism. Since a certain level of skeletal muscle strength is a prerequisite to cope with everyday activities, strength training is recommended as an important part of cardiac rehabilitation.
Assuntos
Envelhecimento/fisiologia , Cardiopatias/fisiopatologia , Força Muscular , Músculo Esquelético/fisiopatologia , Esportes/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braço/fisiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Contração Isométrica , Perna (Membro)/fisiologia , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , TorqueRESUMO
The evolution of novel functional traits can contribute substantially to the diversification of lineages. Older functional traits might show greater variation than more recently evolved novelties, due to the accrual of evolutionary changes through time. However, functional complexity and many-to-one mapping of structure to function could complicate such expectations. In this context, we compared kinematics and performance across juveniles from multiple species for two styles of waterfall-climbing that are novel to gobiid fishes: ancestral "powerburst" climbing, and more recently evolved "inching", which has been confirmed only among species of a single genus that is nested within the clade of powerburst climbers. Similar net climbing speeds across inching species seem, at first, to indicate that this more recently evolved mode of climbing exhibits less functional diversity. However, these similar net speeds arise through different pathways: Sicyopterus stimpsoni from Hawai'i move more slowly than S. lagocephalus from La Réunion, but may also spend more time moving. The production of similar performance between multiple functional pathways reflects a situation that resembles the phenomenon of many-to-one mapping of structure to function. Such similarity has the potential to mask appropriate interpretations of relative functional diversity between lineages, unless the mechanisms underlying performance are explored. More specifically, similarity in net performance between "powerburst" and "inching" styles indicates that selection on climbing performance was likely a limited factor in promoting the evolution of inching as a new mode of climbing. In this context, other processes (e.g., exaptation) might be implicated in the origin of this functional novelty.
FRENCH: Diversité fonctionnelle des innovations évolutives: l'exemple de la cinématique et des performances de grimpe des chutes d'eau des juvéniles de gobies Résumé L'évolution de nouveaux traits fonctionnels peut contribuer significativement à la diversification des lignées. Les traits fonctionnels les plus anciens peuvent montrer plus de variabilité que les plus récents du fait de l'accumulation de changements évolutif au cours du temps. Cependant, ces prédictions peuvent être complexifiées par la diversité des fonctions et par l'implication de plusieurs structures dans une même fonction. Dans ce contexte, nous avons étudié la cinématique et les performances de grimpe des chutes d'eau de plusieurs espèces de gobies utilisant deux styles de grimpe originaux au sein de cette famille: le mode « powerburst ¼ plus ancestral et le mode « inching ¼ qui a évolué plus récemment. Le mode inching n'a été confirmé que pour deux espèces du même genre incluses au sein du clade des powerburst. Des vitesses de grimpe similaires entre les espèces utilisant le mode inching paraissent indiquer que ce mode de grimpe, qui a évolué plus récemment, présente une diversité fonctionnelle moins élevée. Toutefois, la similarité des vitesses de grimpe entre les deux espèces s'explique par des processus différents: le Sicyopterus stimpsoni d'Haiwaï se déplace plus lentement que le S. lagocephalus de La Réunion mais passe plus de temps en mouvement. La production de performances similaires, résultant de processus différents, reflète un phénomène semblable à celui de l'implication de plusieurs structures dans une même fonction. Si les mécanismes sous-jacents ne sont pas explorés, ces similarités peuvent perturber l'interprétation des différences relatives de diversité fonctionnelle entre les lignées. Par ailleurs, les performances de grimpe similaires entre certaines espèces utilisant le mode inching et d'autres le mode powerburst paraissent indiquer que la force de sélection sur les performances de grimpe est sans doute un facteur réduisant l'avantage évolutif du mode de grimpe inching. Dans ce contexte, d'autres mécanismes (e.g., exaptation) pourraient être à l'origine de cette innovation fonctionnelle. Translated to French by Raphael Lagarde (raph.lagarde@gmail.com).
PORTUGESE: Diversidade funcional de novidades evolucionárias: percepções da cinemática da escalada em cascatas e desempenho de peixes juvenis gobiídeos ResumoA evolução de novos traços funcionais pode contribuir substancialmente para a diversificação de linhagens. Os traços funcionais mais antigos podem mostrar maior variação do que as novidades desenvolvidas mais recentemente, devido ao acúmulo de mudanças evolutivas ao longo do tempo. No entanto, a complexidade funcional e os inúmeros mapeamentos de uma estrutura para uma única função podem complicar essas expectativas. Nesse contexto, comparamos a cinemática e a performance em juvenis de várias espécies para dois estilos de escalada em cascata que são novidades em peixes gobiídeos: a ancestral escalada por "explosão" e o evolutivamente mais recente chamado de "avançamento", que foi confirmado apenas entre espécies de um único gênero que dentro do clado de escaladores por explosão. Velocidades finais de escalada semelhantes entre espécies usando "avançamento" parecem, inicialmente, indicar que esse modo de escalada evolutivamente mais recente exibe menor diversidade funcional. No entanto, essas velocidades finais similares ocorrem por diferentes formas: Sicyopterus stimpsoni do Havaí se move mais devagar que S. lagocephalus das Ilhas Reunião, mas pode gastar mais tempo se movendo. Desempenhos semelhantes entre várias vias funcionais refletem uma situação que se assemelha ao fenômeno de mapeamento de uma estrutura para um única função. Essa semelhança tem o potencial de ocultar interpretações apropriadas sobre relativa diversidade funcional entre linhagens, a menos que os mecanismos que afetam o desempenho sejam explorados. Mais especificamente, a semelhança no desempenho final entre os estilos "explosão" e "avançamento"indica que a seleção na performance em escalada provavelmente foi um fator limitante na promoção da evolução por "avançamento" como um novo modo de escalada. Nesse contexto, outros processos (e.g., exaptação) podem estar relacionados com a origem dessa novidade funcional. Translated to Portuguese by Diego Vaz (dbistonvaz@vims.edu).
RESUMO
Bilateral lesions of primary visual cortex (PVC) sustained early in life induce the visual system to undergo structural and functional reorganization and produce modified neuronal networks capable of mediating visual abilities that would be impaired if the lesions occurred in adulthood. Reorganization after early lesion is also accompanied by degeneration of the lateral geniculate nucleus of the thalamus, and 90% of beta retinal ganglion cells die via retrograde degeneration. It is unclear whether the high potential of the system to reorganize after early lesion could overcome the effects of beta retinal ganglion cell death. Visual acuity, which depends on an intact beta-cell array, was impaired in cats that underwent PVC lesions on postnatal day 1 and indicated that neuroplastic potential was insufficient to overcome early lesion-induced maladaptive plasticity. Animals with lesions made at 1 month of age, a stage accompanied by high levels of neuroplastic potential but no death of beta cells, achieved acuity measures equivalent to intact animals. The authors conclude that visual signals are rerouted to subserve functionality when the lesion is made at 1 month of age, but not at 1 day of age.
Assuntos
Envelhecimento/fisiologia , Lateralidade Funcional/fisiologia , Acuidade Visual/fisiologia , Córtex Visual/lesões , Córtex Visual/fisiologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Gatos , Comportamento de Escolha/fisiologia , Discriminação Psicológica/fisiologia , Estatísticas não ParamétricasRESUMO
The backbone torsion angle pair (varphi,psi) at each amino acid of a polypeptide is a descriptor of its conformation. One can use chemical shift and dipolar coupling data from solid-state NMR PISEMA experiments to directly calculate the torsion angles for the membrane-spanning portion of a protein. However, degeneracies inherent in the data give rise to multiple potential torsion angles between two adjacent peptide planes (a diplane). The molecular backbone structure can be determined by gluing together the consecutive diplanes, as in the PIPATH algorithm [T. Asbury, J.R. Quine, S. Achuthan, J. Hu, M.S. Chapman, T.A. Cross, R. Bertram, PIPATH: an optimized alogrithm for generating alpha-helical structures from PISEMA data, J. Magn. Reson. 183 (2006) 87-95.]. The multiplicities in torsion angles translate to multiplicities in diplane orientations. In this paper, we show that adjacent diplanes can be glued together to form a permissible structure only if they satisfy continuity conditions, described quantitatively here. These restrict the number of potential torsion angle pairs. We rewrite the torsion angle formulas from [J.R. Quine, M.T. Brenneman, T.A. Cross, Protein structural analysis from solid-state NMR-drived orientational constraints, Biophys. J. 72 (1997) 2342-2348.] so that they automatically satisfy the continuity conditions. The reformulated torsion angle formulas have been applied recently in the PIPATH algorithm [T. Asbury, J.R. Quine, S. Achuthan, J. Hu, M.S. Chapman, T.A. Cross, R. Bertram, PIPATH: an optimized alogrithm for generating alpha-helical structures from PISEMA data, J. Magn. Reson. 183 (2006) 87-95.] and will be helpful in other applications in which diplane gluing is used to construct a protein backbone model.
Assuntos
Bicamadas Lipídicas/química , Espectroscopia de Ressonância Magnética/métodos , Modelos Químicos , Modelos Moleculares , Proteínas/química , Proteínas/ultraestrutura , Simulação por Computador , Conformação Proteica , Rotação , Estresse MecânicoRESUMO
Visuospatial neglect is a common neurological syndrome caused by unilateral brain damage to the posterior and inferior parietal cerebral cortex, and is characterized by an inability to respond or orient to stimuli presented in the contralesional hemifield. Neglect has been elicited in experimental models of the rat, cat and monkey, and is thought to result in part from a pathological state of inhibition exerted on the damaged hemisphere by the hyperexcited intact hemisphere. We sought to test this theory by assessing neural activity levels in multiple brain structures during neglect using 2-deoxyglucose (2DG) as a metabolic marker of neural activity. Neglect was induced in two ways: (i) by cooling deactivation of posterior parietal cortex or (ii) in conjunction with broader cortical blindness produced by unilateral lesion of all contiguous visual cortical areas spanning occipital, parietal and temporal regions. The direction and magnitude of changes in 2DG uptake were measured in cerebral cortex and midbrain structures. Finally, the 2DG uptake was assessed in a group of cats in which the lesion-induced neglect component of blindness was cancelled by cooling of either the contralateral posterior parietal cortex or the contralateral superior colliculus (SC). Overall, we found that (i) both lesion- and cooling-induced neglect are associated with decreases in 2DG uptake in specific ipsilateral cortical and midbrain regions; (ii) levels of 2DG uptake in the intermediate and deep layers of the SC contralateral to both cooling and lesion deactivations are increased; (iii) changes in 2DG uptake were not identified in the contralateral cortex; and (iv) reversal of the lesion-induced neglect component of blindness is associated with a reduction of contralesional 2DG uptake to normal or subnormal levels. These data are in accord with theories of neglect that include mutually suppressive mechanisms between the two hemispheres, and we show that these mechanisms operate at the level of the SC, but are not apparent at the level of cortex. These results suggest that the most effective therapies for visual neglect will be those that act to decrease neural activity in the intermediate layers of the SC contralateral to the brain damage.
Assuntos
Lobo Parietal/fisiopatologia , Transtornos da Percepção/fisiopatologia , Colículos Superiores/fisiopatologia , Animais , Cegueira Cortical/etiologia , Cegueira Cortical/fisiopatologia , Mapeamento Encefálico/métodos , Gatos , Temperatura Baixa , Desoxiglucose , Modelos Animais de Doenças , Percepção de Movimento , Transtornos da Percepção/psicologia , Testes de Campo Visual/métodosRESUMO
We present the first-time growth of bulk BaSnO3 single crystals from the melt by direct solidification, their basic electrical and optical properties as well as their structural quality. Our measurement of the melting point (MP) of BaSnO3 amounts to 1855 °C ± 25 K. At this temperature an intensive decomposition and non-stoichiometric evaporation takes place as the partial pressure of SnO(g) is about 90 times higher than that of BaO(g). X ray powder diffraction identified only the BaSnO3 perovskite phase, while narrow rocking curves having a full width at half maximum of 26 arcsec and etch pit densities below 106 cm-2 confirm a high degree of structural perfection of the single crystals. In this respect they surpass the structural properties of those single crystals that were reported in the literature. The electrical conductivity of nominally undoped crystals depends on the growth conditions and ranges from insulating to medium n-type conductivity. After post-growth annealing in an oxidizing atmosphere undoped crystals are generally insulating. Doping the crystals with lanthanum during growth results in a high n-type conductivity. For a La doping concentration of 0.123 wt.% we measured an electron concentration of 3.3 × 1019 cm-3 and an electron mobility of 219 cm2 V-1 s-1. Based on optical absorption measurements we determined an energy of 3.17 ± 0.04 eV at 5 K and of 2.99 ± 0.04 eV at 297 K for the indirect band gap of BaSnO3.
RESUMO
An optimized algorithm for finding structures and assignments of solid-state NMR PISEMA data obtained from alpha-helical membrane proteins is presented. The description of this algorithm, PIPATH, is followed by an analysis of its performance on simulated PISEMA data derived from synthetic and experimental structures. pipath transforms the assignment problem into a path-finding problem for a directed graph, and then uses techniques of graph theory to efficiently find candidate assignments from a very large set of possibilities.
Assuntos
Algoritmos , Espectroscopia de Ressonância Magnética/métodos , Proteínas de Membrana/química , Proteínas de Membrana/ultraestrutura , Modelos Químicos , Modelos Moleculares , Estrutura Secundária de Proteína , Simulação por Computador , Cristalografia , Marcadores de SpinRESUMO
The solid-state NMR experiment PISEMA, is a technique for determining structures of proteins, especially membrane proteins, from oriented samples. One method for determining the structure is to find orientations of local molecular frames (peptide planes) with respect to the unit magnetic field direction, B0. This is done using equations that compute the coordinates of this vector in the frames. This requires an analysis of the PISEMA function and its degeneracies. As a measure of the sensitivity of peptide plane orientations to the data, we use these equations to derive a formula for the intensity function in the powder pattern. With this function and other measures, we investigate the effect of small changes in peptide plane orientations depending on the location of the resonances in the powder pattern spectrum. This gives us an indication of the change in lineshape due to mosaic spread and a way to interpret these in terms of an orientational error bar.
Assuntos
Canais Iônicos/química , Ressonância Magnética Nuclear Biomolecular/métodos , Proteínas/química , Estrutura MolecularRESUMO
The functional relationships between the primary visual cortex and its major subcortical target structures have long been a subject of interest. We studied these relationships by using localized cooling deactivation to silence portions of primary visual cortex and measuring 2-deoxyglucose (2DG) uptake to assess neural activity in subcortical and midbrain targets. We focused analysis on the largest subcortical targets of primary visual cortex: the superior colliculus (SC), the dorsal lateral geniculate nucleus of the thalamus (dLGN), and the lateral division of the lateral posterior nucleus of the thalamus (LPL). We found that localized cooling of different regions of primary visual cortex caused specific decreases in 2DG uptake in target structures such that the location of 2DG decrease varied according to joint retinotopy, and the magnitude of the decreases in target structures was associated with the amount of cooled cortex. In addition, we found that the impact of cortical cooling was more profound on the SC than on the dLGN. The functional impact of cortical deactivations on the LPL was weak for small deactivations but approximated the impact on the SC when deactivations were large. We discuss these findings in terms of neural circuits and in terms of drivers and modulators.
Assuntos
Mapeamento Encefálico , Corpos Geniculados/fisiologia , Colículos Superiores/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Gatos , Corpos Geniculados/citologia , Neurônios/fisiologia , Colículos Superiores/citologia , Córtex Visual/citologia , Vias Visuais/citologiaRESUMO
A novel calcium-dependent potassium current (K(slow)) that slowly activates in response to a simulated islet burst was identified recently in mouse pancreatic beta-cells (Göpel, S.O., T. Kanno, S. Barg, L. Eliasson, J. Galvanovskis, E. Renström, and P. Rorsman. 1999. J. Gen. Physiol. 114:759-769). K(slow) activation may help terminate the cyclic bursts of Ca(2+)-dependent action potentials that drive Ca(2+) influx and insulin secretion in beta-cells. Here, we report that when [Ca(2+)](i) handling was disrupted by blocking Ca(2+) uptake into the ER with two separate agents reported to block the sarco/endoplasmic calcium ATPase (SERCA), thapsigargin (1-5 microM) or insulin (200 nM), K(slow) was transiently potentiated and then inhibited. K(slow) amplitude could also be inhibited by increasing extracellular glucose concentration from 5 to 10 mM. The biphasic modulation of K(slow) by SERCA blockers could not be explained by a minimal mathematical model in which [Ca(2+)](i) is divided between two compartments, the cytosol and the ER, and K(slow) activation mirrors changes in cytosolic calcium induced by the burst protocol. However, the experimental findings were reproduced by a model in which K(slow) activation is mediated by a localized pool of [Ca(2+)] in a subspace located between the ER and the plasma membrane. In this model, the subspace [Ca(2+)] follows changes in cytosolic [Ca(2+)] but with a gradient that reflects Ca(2+) efflux from the ER. Slow modulation of this gradient as the ER empties and fills may enhance the role of K(slow) and [Ca(2+)] handling in influencing beta-cell electrical activity and insulin secretion.
Assuntos
Cálcio/metabolismo , Citoplasma/metabolismo , Ilhotas Pancreáticas/metabolismo , Canais de Potássio Cálcio-Ativados/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Células Cultivadas , Citoplasma/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , CamundongosRESUMO
Free-beam interferometry and angle-resolved absorption spectra are used to investigate the linear electro-optic coefficients and the linear dichroism in photoaddressable bis-azo copolymer thin films. From the first- and second order parameters deduced, the chromophore orientation distribution is calculated and displayed for several poling temperatures and chromophore concentrations. The influence of dipole-dipole interaction on the overall polymer dynamics is discussed. The first order parameter, and therefore the Pockels effect, peaks for a poling temperature of around 10 degrees C above the glass transition. The decrease of the Pockels effect above this temperature region is triggered by a head-to-tail chromophore orientation, i.e., a transition to a microcrystalline phase, increasing the second order parameter. Comparison of the experimentally observed absorption spectra and those obtained by density-functional calculations support the picture of differently aligned bis-azo dye molecules in a trans,trans configuration. Complementary wide-angle x-ray scattering is recorded to confirm the various kinds of ordering in samples poled at different temperatures.
Assuntos
Compostos Azo/química , Corantes Fluorescentes/química , Interferometria , Membranas Artificiais , Modelos Químicos , Algoritmos , Compostos Azo/análise , Dicroísmo Circular , Simulação por Computador , Eletroquímica , Corantes Fluorescentes/análise , Teste de Materiais , Difração de Raios XRESUMO
Nanoscopic yttrium acetate fluorides Y(CH(3)COO)(3-z)F(z) and yttrium oxide fluorides YO(3-z)/(2)F(z )were prepared with tunable Y/F molar ratios via the fluorolytic sol-gel route. All samples were characterized by X-ray diffraction, elemental analysis and thermal analysis. In addition, local structures of all samples were studied by (19)F MAS, (19)F-(89)Y CP MAS and (1)H-(89)Y CP MAS NMR spectroscopy and the respective chemical shifts are given. For both classes of compounds, only the fluorination using one equivalent of F (z = 1) leads to defined, well crystalline matrices: yttrium acetate fluoride Y(CH(3)COO)(2)F and r-YOF.
RESUMO
The purpose of this perspective is twofold: 1) to alert and inform the neurospychology and neurology communities on how animal models can improve our understanding of spatial neglect in humans, and 2) to serve as a guide to rehabilitation strategies. Spatial neglect is a neurological syndrome that is inextricably linked to the ability to overtly or covertly reorient attention to new loci. Literature describing variants of neglect leads to the perception of lesion-induced neglect as a uniquely human syndrome for which there are limited treatment options. To the contrary, neglect has been reversed in laboratory animals, and results show that adequate neural representations and motor mechanisms for reversal are present despite damaged or deactivated cerebral cortex. These results and conclusions provoke thought on strategies that can be employed on humans to cancel neglect, and they suggest that long-term amelioration of neglect can be induced by training of specific bypass circuits.
Assuntos
Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Extinção Psicológica/fisiologia , Transtornos da Percepção/fisiopatologia , Animais , HumanosRESUMO
The repercussions of localized injury of the cerebral cortex in young brains differ from the repercussions triggered by equivalent damage of the mature brain. In the young brain, some distant neurons are more vulnerable to the lesion, whereas others survive and expand their projections to bypass damaged and degenerated structures. The net result is sparing of neural processing and behaviors. This article summarizes both the modifications in visual pathways resulting from visual cortex lesions sustained early in life and the neural and behavioral processes that are spared or permanently impaired. Experiments using reversible deactivation show that at least two highly localizable functions of normal cerebral cortex are remapped across the cortical surface as a result of an early lesion of the primary visual cortex. Moreover, the redistributions have spread the essential neural operations underlying orienting behavior from the visual parietal cortex to a normally functionally distinct type of cortex in the visual temporal system, and in the opposite direction for complex-pattern recognition. Similar functional reorganizations may underlie sparing of neural processes and behavior following early lesions in other cerebral systems, and these other systems may respond well to emerging therapeutic strategies designed to enhance the sparing of functions.
Assuntos
Envelhecimento/fisiologia , Plasticidade Neuronal , Córtex Visual/lesões , Vias Visuais/lesões , Animais , Humanos , Plasticidade Neuronal/fisiologia , Córtex Visual/fisiopatologia , Vias Visuais/fisiopatologiaRESUMO
In humans, damage to posterior parietal or frontal cortices often induces a severe impairment of the ability to redirect gaze to visual targets introduced into the contralateral field. In cats, unilateral deactivation of the posterior middle suprasylvian (pMS) sulcus in the posterior inferior parietal region also results in an equally severe impairment of visually mediated redirection of gaze. In this study we tested the contributions of the pMS cortex and 14 other cortical regions in mediating redirection of gaze to visual targets in 31 adult cats. Unilateral cooling deactivation of three adjacent regions along the posterior bend of the suprasylvian sulcus (posterior middle suprasylvian sulcus, posterior suprasylvian sulcus, and dorsal posterior ectosylvian gyrus at the confluence of the occipital, parietal, and temporal cortices) eliminated visually mediated redirection of gaze towards stimuli introduced into the contralateral hemifield, while the redirection of gaze toward the ipsilateral hemifield remained highly proficient. Additional cortical loci critical for visually mediated redirection of gaze include the anterior suprasylvian gyrus (lateral area 5, anterior inferior parietal cortex) and medial area 6 in the frontal region. Cooling deactivation of: 1) dorsal or 2) ventral posterior suprasylvian gyrus; 3) ventral posterior ectosylvian gyrus, 4) middle ectosylvian gyrus; 5) anterior or 6) posterior middle suprasylvian gyrus (area 7); 7) anterior middle suprasylvian sulcus; 8) medial area 5; 9) the visual portion of the anterior ectosylvian sulcus (AES); 10) or lateral area 6 were all without impact on the ability to redirect gaze. In summary, we identified a prominent field of cortex at the junction of the temporo-occipito-parietal cortices (regions pMS, dPE, PS), an anterior inferior parietal field (region 5L), and a frontal field (region 6M) that all contribute critically to the ability to redirect gaze to novel stimuli introduced into the visual field during fixation. These loci have several features in common with cortical fields in monkey and human brains that contribute to the visually guided redirection of the head and eyes.
Assuntos
Mapeamento Encefálico , Movimentos da Cabeça/fisiologia , Lobo Parietal/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Animais , Comportamento Animal , Gatos , Temperatura Baixa , Humanos , FilogeniaRESUMO
Burst firing of dopaminergic neurons of the substantia nigra pars compacta can be induced in vitro by the glutamate agonist N-methyl-D-aspartate. It has been suggested that the interburst hyperpolarization is due to Na+ extrusion by a ouabain-sensitive pump [Johnson et al. (1992) Science 258, 665-667]. We formulate and explore a theoretical model, with a minimal number of currents, for this novel mechanism of burst generation. This minimal model is further developed into a more elaborate model based on observations of additional currents and hypotheses about their spatial distribution in dopaminergic neurons [Hounsgaard (1992) Neuroscience 50, 513-518; Llinás et al. (1984) Brain Res. 294, 127-132]. Using the minimal model, we confirm that interaction between the regenerative, inward N-methyl-D-aspartate-mediated current and the outward Na(+)-pump current is sufficient to generate the slow oscillation (approximately 0.5 Hz) underlying the burst. The negative-slope region of the N-methyl-D-aspartate channel's current-voltage relation is indispensable for this slow rhythm generation. The time-scale of Na(+)-handling determines the burst's slow frequency. Moreover, we show that, given the constraints of sodium handling, such bursting is best explained mechanistically by using at least two spatial, cable-like compartments: a soma where action potentials are produced and a dendritic compartment where the slow rhythm is generated. Our result is consistent with recent experimental evidence that burst generation originates in distal dendrites [Seutin et al. (1994) Neuroscience 58, 201-206]. Responses of the model to a number of electrophysiological and pharmacological stimuli are consistent with known responses observed under similar conditions. These include the persistence of the slow rhythm when the tetrodotoxin-sensitive Na+ channel is blocked and when the soma is voltage-clamped at -60 mV. Using our more elaborate model, we account for details of the observed frequency adaptation in N-methyl-D-aspartate-induced bursting, the origin of multiple spiking and bursting mechanisms, and the interaction between two different bursting mechanisms. Besides reproducing several well established firing patterns, this model also suggests that new firing modes, not yet recorded, might also occur in dopaminergic neurons. This model provides mechanistic insights and explanations into the origin of a variety of experimentally observed membrane potential firing patterns in dopaminergic neurons, including N-methyl-D-aspartate-induced bursting and its dendritic origin. Such a model, capable of reproducing a number of realistic behaviors of dopaminergic neurons, could be useful in further studies of the basal ganglia-thalamocortical motor circuit. It may also shed light on bursting that involves N-methyl-D-aspartate channel activity in other neuron types.