A proposed mechanism for the sol-gel transformation

The transformation from gel to sol in cell cytoplasm is treated as the transition from a lattice of macromolecules linked by Ca⁺⁺ ions to a random distribution of the macromolecules. The transition is a cooperative process, whose probability is expressed in terms of the theory of runs. The process is related to cell metabolism by the assumption that available Ca⁺⁺ concentration is regulated by metabolically produced endogenous chelating agents. Contribution 681 from the Division of Basic Health Sciences, Emory University.     

A proposed mechanism for the catalatic action of catalase

A detailed mechanism for catalatic action has been proposed which includes the formation of Chance's catalase compound I in the first step and hydride ion transfer in the second step. The first (oxidative) step involves direct reaction of hematin iron with an ionized H2O2 molecule, followed by an oxidation of the iron to Fe IV. The second step is assumed to depend upon the reductive action of a second H2O2 molecule on Chance's compound I through a catalyzed hybride ion transfer, resulting in the regeneration of uncomplexed catalase. Differences between the catalatic and peroxidative actions of catalase are discussed briefly in respect to the proposed mechanism for catalatic action. The rationale of the proposed mechanism is based to a considerable extent upon the type of ligand binding by the hematin iron of catalase, and this type of ligand bonding is contrasted with ligand binding in methemoglobin, which does not show catalatic activity. Finally, the dispositions of electrons in the outer electronic orbitals of the hematin iron of catalase and methemoglobin are discussed, as a means of justifying formulae presented for catalase and methemoglobin and their derivatives. One of the features of the proposed catalatic mechanism is the assumption, based on electron spin number, that the sixth coordination position around the hematin iron of uncomplexed catalase is unoccupied.     

A proposed mechanism for myosin magnesium adenosine triphosphatase activity

A formal mechanism for the myosin MgATPase is proposed. The basic characteristics of this mechanism require that the binding of substrate at either one of two equivalent nucleotide sites of uncomplexed myosin prevents binding of substrate at the other unoccupied site (i.e. negative cooperativity) and that the rapid formation of a myosin-product complex permits binding of substrate at the unoccupied site. Analogue computer kinetic simulations indicate that the proposed mechanism is compatible with the observed transient phase kinetics characterizing the interaction of the enzyme with MgATP. In addition, analysis of the derived rate equation show that the mechanism is also consistent with existing steady-state kinetic data for the myosin MgATPase. A simpler mechanism is proposed for the subfragment-1 MgATPase that is shown to be compatible with the existing kinetic data. Features of the proposed myosin MgATPase mechanism are incorporated into a model of contraction which utilizes the bipartite structure and nucleotide site interaction of the myosin crossbridge to provide an efficient utilization of ATP in the contraction cycle.     

A proposed neural network for the integrator of the oculomotor system

Single-unit recordings, stimulation studies, and eye movement measurements all indicate that the firing patterns of many oculomotor neurons in the brain stem encode eye-velocity commands in premotor circuits while the firing patterns of extraocular motoneurons contain both eye-velocity and eye-position components. It is necessary to propose that the eye-position component is generated from the eye-velocity signal by a leaky hold element or temporal integrator. Prior models of this integrator suffer from two important problems. Since cells appear to have a steady, background signal when eye position and velocity are zero, how does the integrator avoid integrating this background rate? Most models employ some form of lumped, oositive feedback the gain of which must be kept within totally unreasonable limits for proper operation. We propose a lateral inhibitory network of homogeneous neurons as a model for the neural integrator that solves both problems. Parameter sensitivity studies and lesion simulations are presented to demonstrate robustness of the model with respect to both the choice of parameter values and the consequences of pathological changes in a portion of the neural integrator pool.     

A proposed mechanism of thermophily in facultative thermophiles

Glyceraldehyde-3-phosphate dehydrogenase in crude extracts of $\text{Bacillus coagulans}$ KU, a facultative thermophile, showed marked thermolability whether the cells were grown at mesophilic or thermophilic temperature. When extracts were brought to a given ionic strength by the addition of salt and then heat treated, it was possible to confer heat resistance well in excess of the thermophilic growth temperature. Disc electrophoresis is indicative that portions of the profiles are quite different between extracts of cells grown at 37° and 55°. Based on the data, a mechanism of thermophily is postulated that is different from any thus far proposed for thermophilic microorganisms.     

A proposed proton shuttle mechanism for saccharopine dehydrogenase from Saccharomyces cerevisiae

Saccharopine dehydrogenase [N6-(glutaryl-2)-L-lysine:NAD oxidoreductase (L-lysine forming)] catalyzes the final step in the alpha-aminoadipate pathway for lysine biosynthesis. It catalyzes the reversible pyridine nucleotide-dependent oxidative deamination of saccharopine to generate alpha-Kg and lysine using NAD+ as an oxidizing agent. The proton shuttle chemical mechanism is proposed on the basis of the pH dependence of kinetic parameters, dissociation constants for competitive inhibitors, and isotope effects. In the direction of lysine formation, once NAD+ and saccharopine bind, a group with a pKa of 6.2 accepts a proton from the secondary amine of saccharopine as it is oxidized. This protonated general base then does not participate in the reaction again until lysine is formed at the completion of the reaction. A general base with a pKa of 7.2 accepts a proton from H2O as it attacks the Schiff base carbon of saccharopine to form the carbinolamine intermediate. The same residue then serves as a general acid and donates a proton to the carbinolamine nitrogen to give the protonated carbinolamine. Collapse of the carbinolamine is then facilitated by the same group accepting a proton from the carbinolamine hydroxyl to generate alpha-Kg and lysine. The amine nitrogen is then protonated by the group that originally accepted a proton from the secondary amine of saccharopine, and products are released. In the reverse reaction direction, finite primary deuterium kinetic isotope effects were observed for all parameters with the exception of V2/K(NADH), consistent with a steady-state random mechanism and indicative of a contribution from hydride transfer to rate limitation. The pH dependence, as determined from the primary isotope effect on DV2 and D(V2/K(Lys)), suggests that a step other than hydride transfer becomes rate-limiting as the pH is increased. This step is likely protonation/deprotonation of the carbinolamine nitrogen formed as an intermediate in imine hydrolysis. The observed solvent isotope effect indicates that proton transfer also contributes to rate limitation. A concerted proton and hydride transfer is suggested by multiple substrate/solvent isotope effects, as well as a proton transfer in another step, likely hydrolysis of the carbinolamine. In agreement, dome-shaped proton inventories are observed for V2 and V2/K(Lys), suggesting that proton transfer exists in at least two sequential transition states.     

A proposed mechanism for the potentiation of cAMP-mediated acid secretion by carbachol

Acid secretion in isolated rabbit gastric glands was monitored by the accumulation of [(14)C]aminopyrine. Stimulation of the glands with carbachol synergistically augmented the response to dibutyryl cAMP. The augmentation persisted even after carbachol was washed out and was resistant to chelated extracellular Ca(2+) and to inhibitors of either protein kinase C or calmodulin kinase II. Cytochalasin D at 10 microM preferentially blocked the secretory effect of carbachol and its synergism with cAMP, whereas it had no effect on histamine- or cAMP-stimulated acid secretion within 15 min. Cytochalasin D inhibited the carbachol-stimulated intracellular Ca(2+) concentration ([Ca(2+)](i)) increase due to release from the Ca(2+) store. Treatment of the glands with cytochalasin D redistributed type 3 inositol 1,4,5-trisphosphate receptor (the major subtype in the parietal cell) from the fraction containing membranes of large size to the microsomal fraction, suggesting a dissociation of the store from the plasma membrane. These findings suggest that intracellular Ca(2+) release by cholinergic stimulation is critical for determining synergism with cAMP in parietal cell activation and that functional coupling between the Ca(2+) store and the receptor is maintained by actin microfilaments.     

A review on directional information in neural signals for brain-machine interfaces

Brain-machine interfaces (BMIs) can be characterized by the technique used to measure brain activity and by the way different brain signals are translated into commands that control an effector. We give an overview of different approaches and focus on a particular BMI approach: the movement of an artificial effector (e.g. arm prosthesis to the right) by those motor cortical signals that control the equivalent movement of a corresponding body part (e.g. arm movement to the right). This approach has been successfully applied in monkeys and humans by accurately extracting parameters of movements from the spiking activity of multiple single-units. Here, we review recent findings showing that analog neuronal population signals, ranging from intracortical local field potentials over epicortical ECoG to non-invasive EEG and MEG, can also be used to decode movement direction and continuous movement trajectories. Therefore, these signals might provide additional or alternative control for this BMI approach, with possible advantages due to reduced invasiveness.     

A neural network model for the mechanism of feature-extraction

We propose a new multilayered neural network model which has the ability of rapid self-organization. This model is a modified version of the cognitron (Fukushima, 1975). It has modifiable inhibitory feedback connections, as well as conventional modifiable excitatory feedforward connections, between the cells of adjoining layers. If a feature-extracting cell in the network is excited by a stimulus which is already familiar to the network, the cell immediately feeds back inhibitory signals to its presynaptic cells in the preceding layer, which suppresses their response. On the other hand, the feature-extracting cell does not respond to an unfamiliar feature, and the responses from its presynaptic cells are therefore not suppressed because they do not receive any feedback inhibition. Modifiable synapses in the new network are reinforced in a way similar to those in the cognitron, and synaptic connections from cells yielding a large sustained output are reinforced. Since familiar stimulus features do not elicit a sustained response from the cells of the network, only circuits which detect novel stimulus features develop. The network therefore quickly acquires favorable pattern-selectivity by the mere repetitive presentation of set of learning patterns.     

A neural mechanism for the immediate recall of sequences

Summary Lashley's suggestion that serial behavior has a dual organization, central facilitation of the entire sequence plus scanning of the individual movements, is taken as the starting point for the construction of a model to illustrate in more detail how the nervous system might work during such behavior.Two stages in the learning of a sequence are distinguished: 1. immediate reproduction of a presented sample, and 2. reproduction of habitual responses by association, without the necessity of recent access to the original sample. The model is primarily concerned with performances of the first type.Neurons of a scanning chain, which always fire one another in the same order, acquire temporary connections with the movements to be recalled. The connections fade rapidly with disuse so that the same scanning chain can be used again with different combinations of movements.The same mechanism will also permit the recall of sequences of words, or other habitual movement complexes, as if they were individual movements. It is assumed that such habitual motor patterns as words are under the control of higher-order cell assemblies which regulate the sequences of movements within the response, and thus substitute for the general scanning mechanism. This leaves the scanner free to form temporary associations with the higher-order cell assemblies for the words.It is suggested that the scanning mechanism is actuated only by unpredictable inputs so that the elements within a habitual series do not acquire unnecessary connections with the scanning neurons. The arousal system is known to have this characteristic of not being disturbed by the expected, and it seems likely that the two systems are intimately related.     

神经电生理信号多道同步采集和分析系统

单细胞多点同步记录技术在国内外已经被广泛应用,但在国内仍缺乏与国产或日产细胞电生理记录仪器相匹配的多通道同步生物电信号采集与分析系统。本文介绍了新近研制的可进行双通道甚至晚多通道细胞电生理信号采集的神经细胞电生理信号采集与分析系统,及其关键技术及实现方法和应用实例。     

A potential neural substrate for processing functional classes of complex acoustic signals

Categorization is essential to all cognitive processes, but identifying the neural substrates underlying categorization processes is a real challenge. Among animals that have been shown to be able of categorization, songbirds are particularly interesting because they provide researchers with clear examples of categories of acoustic signals allowing different levels of recognition, and they possess a system of specialized brain structures found only in birds that learn to sing: the song system. Moreover, an avian brain nucleus that is analogous to the mammalian secondary auditory cortex (the caudo-medial nidopallium, or NCM) has recently emerged as a plausible site for sensory representation of birdsong, and appears as a well positioned brain region for categorization of songs. Hence, we tested responses in this non-primary, associative area to clear and distinct classes of songs with different functions and social values, and for a possible correspondence between these responses and the functional aspects of songs, in a highly social songbird species: the European starling. Our results clearly show differential neuronal responses to the ethologically defined classes of songs, both in the number of neurons responding, and in the response magnitude of these neurons. Most importantly, these differential responses corresponded to the functional classes of songs, with increasing activation from non-specific to species-specific and from species-specific to individual-specific sounds. These data therefore suggest a potential neural substrate for sorting natural communication signals into categories, and for individual vocal recognition of same-species members. Given the many parallels that exist between birdsong and speech, these results may contribute to a better understanding of the neural bases of speech.     

A proposed mechanism for the lowering of mitochondrial electron leak by caloric restriction

Caloric restriction (CR) of laboratory rodents, which extends their maximum lifespan, only transiently reduces the specific metabolic rate of highly oxidative tissues. However, superoxide production by mitochondria of those tissues is greatly reduced by CR. This is probably a major contributor to the slowed aging seen in CR, but its mechanism is unknown. Here it is proposed that the major metabolic shift enabling reduced superoxide production is a diversion of much of the electron flux generated by glycolysis and the TCA cycle away from its usual destination, Complex I, and to the plasma membrane redox system. The cell's ATP synthesis capacity is thereby diminished, but so is its ATP demand, due to reduced turnover of the Na+/K+-ATPase. Direct tests of this hypothesis are proposed.     

A proposed neural pathway for vocalization in South African clawed frogs,Xenopus laevis

Vocalizations of South African clawed frogs are produced by contractions of laryngeal muscles innervated by motor neurons of the caudal medulla (within cranial nerve nucleus IX-X). We have traced afferents to laryngeal motor neurons in male and female frogs using retrograde axonal transport of horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA). After iontophoretic injection of HRP-WGA into n. IX-X, retrogradely labelled neurons were seen in the contralateral n. IX-X, in rhombencephalic reticular nuclei, and in the pre-trigeminal nucleus of the dorsal tegmental area (DTAM) of both males and females.