Interactions between intracellular Ca2+ stores: Ca2+ released from the NAADP pool potentiates cADPR-induced Ca2+ release

Cells possess multiple intracellular Ca2+-releasing systems. Sea urchin egg homogenates are a well-established model to study intracellular Ca2+ release. In the present study the mechanism of interaction between three intracellular Ca2+ pools, namely the nicotinic acid adenine dinucleotide phosphate (NAADP), the cyclic ADP-ribose (cADPR) and the inositol 1',4',5'-trisphosphate (IP3)-regulated Ca2+ stores, is explored. The data indicate that the NAADP Ca2+ pool could be used to sensitize the cADPR system. In contrast, the IP3 pool was not affected by the Ca2+ released by NAADP. The mechanism of potentiation of the cADPR-induced Ca2+ release, promoted by Ca2+ released from the NAADP pool, is mediated by the mechanism of Ca2+-induced Ca2+ release. These data raise the possibility that the NAADP Ca2+ store may have a role as a regulator of the cellular sensitivity to cADPR.

Differential evolution based classification with pool of distances and aggregation operators

The objective of this thesis is to develop and generalize further the differential evolution based data classification method. For many years, evolutionary algorithms have been successfully applied to many classification tasks. Evolution algorithms are population based, stochastic search algorithms that mimic natural selection and genetics. Differential evolution is an evolutionary algorithm that has gained popularity because of its simplicity and good observed performance. In this thesis a differential evolution classifier with pool of distances is proposed, demonstrated and initially evaluated. The differential evolution classifier is a nearest prototype vector based classifier that applies a global optimization algorithm, differential evolution, to determine the optimal values for all free parameters of the classifier model during the training phase of the classifier. The differential evolution classifier applies the individually optimized distance measure for each new data set to be classified is generalized to cover a pool of distances. Instead of optimizing a single distance measure for the given data set, the selection of the optimal distance measure from a predefined pool of alternative measures is attempted systematically and automatically. Furthermore, instead of only selecting the optimal distance measure from a set of alternatives, an attempt is made to optimize the values of the possible control parameters related with the selected distance measure. Specifically, a pool of alternative distance measures is first created and then the differential evolution algorithm is applied to select the optimal distance measure that yields the highest classification accuracy with the current data. After determining the optimal distance measures for the given data set together with their optimal parameters, all determined distance measures are aggregated to form a single total distance measure. The total distance measure is applied to the final classification decisions. The actual classification process is still based on the nearest prototype vector principle; a sample belongs to the class represented by the nearest prototype vector when measured with the optimized total distance measure. During the training process the differential evolution algorithm determines the optimal class vectors, selects optimal distance metrics, and determines the optimal values for the free parameters of each selected distance measure. The results obtained with the above method confirm that the choice of distance measure is one of the most crucial factors for obtaining higher classification accuracy. The results also demonstrate that it is possible to build a classifier that is able to select the optimal distance measure for the given data set automatically and systematically. After finding optimal distance measures together with optimal parameters from the particular distance measure results are then aggregated to form a total distance, which will be used to form the deviation between the class vectors and samples and thus classify the samples. This thesis also discusses two types of aggregation operators, namely, ordered weighted averaging (OWA) based multi-distances and generalized ordered weighted averaging (GOWA). These aggregation operators were applied in this work to the aggregation of the normalized distance values. The results demonstrate that a proper combination of aggregation operator and weight generation scheme play an important role in obtaining good classification accuracy. The main outcomes of the work are the six new generalized versions of previous method called differential evolution classifier. All these DE classifier demonstrated good results in the classification tasks.

Synaptic vesicle pool size, release probability and synaptic depression are sensitive to Ca2+ buffering capacity in the developing rat calyx of Held

The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca2+ buffer capacity. We propose that, during development, a population of vesicles that are tightly coupled to Ca2+ channels expands at the expense of vesicles more distant from Ca2+ channels.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.

Pool Plans

Herb de Bray standing at the edge of the soon to be completed pool of the Elanor Misner Aquatic Center.

Empty Pool

The Brock pool as it begins to be filled with water.

Pool Foundation

Exposed escarpment rock during the construction of the pool.

Pool Filling

Olympic size swimming pool gets filled with water.

Pool

Olympic size swimming pool in the Eleanor Misener Aquatic Centre.

Brock Pool

View of the pool inside the Eleanor Misener Aquatic Centre.

Reliability of a new measure of motoneuron excitability

Objectlve:--This study examined the intraclass reliability· of different measures of the excitability of the Hoffmann reflex, derived from stimulus-response curves. The slope of the regression line of the H-reflex stimulus-response curve advocated by Funase et al. (1994) was also compared to the peak of the first derivative of the H-reflex stimulus-response curve (dHIdVmax), a new measure introduced in this investigation. A secondary purpose was to explore the possibility of mood as a covariate when measuring excitability of the H-reflex arc. Methods: The H-reflex amplitude at a stimulus intensity corresponding to 5% of the maximum M-wave (Mmax) is an established measure that was used as an additional basis of comparison. The H-reflex was elicited in the soleus for 24 subjects (12 males and 12 females) on five separate days. Vibration was applied to the Achilles tendon prior to stimulation to test the sensitivity of the measures on test day four. The means of five evoked potentials at each gradually increasing intensity, from below H-reflex threshold to above Mmax, were used to create both the H-reflex and M-wave stimulus response curves for each subject across test days. The mood of the subjects was assessed using the Subjective Exercise Experience Scale (SEES) prior to the stimulation protocol each day. Results: There was a modest decrease in all H-reflex measures from the first to third test day, but it was non-significant (P's>0.05). All measures of the H-reflex exhibited a profound reduction following vibration on test day four, and then returned to baseline levels on test day five (P's<0.05). The intraclass correlation coefficient (ICC) for H-reflex amplitude at 5% of Mmax was 0.85. The ICC for the slope of the regression line was 0.79 while it was 0.89 for dH/dVmax. Maximum M-wave amplitude had an ICC of 0.96 attesting to careful methodological controls. The SEES subscales of fatigue and psychological well-being remained unchanged IV across the five days. The psychological distress subscale (PO.05). Conclusions: The peak of the first derivative of the H-reflex stimulus-response curve (dH/dVmax) was shown to have comparable reliability and sensitivity to other more established measures of excitability. Psychological distress and the amplitude of the H-reflex at 5% Mmax follow similar trends across days, however there was no significant correlation between the two measures. Significance: The proposed method appears to be a more robust measure ofH-reflex excitability than the other methods tested. As such it would be an advantageous method to apply in clinical and investigative settings. Additionally, the results suggest that the relationship between psychological distress and H-reflex amplitude should be investigated further.

Swimming pool for Cheverton Residence Hall [originally East Hall], Chapman College, Orange, California

Swimming pool area for Cheverton Residence Hall [originally East Hall], Chapman College, Orange, California, ca. 1978.

Pool area, Cheverton Residence Hall [originally East Hall], Chapman College, Orange, California

Around the pool area, Cheverton Residence Hall [originally East Hall], Chapman University, Orange, California, ca. 1978. Dedicated in 1959 and torn down in 2002.