Learning of sequential movements in the monkey: process of learning and retention of memory

1. To characterize procedural learning and memory, we devised a behavioral paradigm that allows us to examine the process of learning of new procedures, repeatedly and without serious difficulties for primate subjects. We trained two monkeys to perform a sequential button press task. Upon pressing of a home key, 2 of 16 (4 x 4 matrix) light-emitting diode (LED) buttons (called "set") were illuminated simultaneously, and the monkey had to press them in a predetermined order that he had to find out by trial-and-error. A total of five sets (called "hyperset") was presented in a fixed order for completion of a trial; an error at any set aborted the trial. A given hyperset was repeated as a block of experiment until 20 successful trials were performed. Monkeys PI and BO experienced 313 and 92 hypersets, respectively. Most of these hypersets were experienced only once (1 block of experiment); the others (28 hypersets for monkey PI and 14 hypersets for monkey BO) were chosen for extensive practice. 2. The learning, indicated as the decrease in the number of trials to criterion and the decrease in the performance time, proceeded at three levels: 1) short-term and sequence-selective learning that occurred by repeating a particular hyperset during a block of experiment; our monkeys learned, to some degree, to perform a new hyperset within a short period (< 5 min); 2) long-term and sequence-selective learning that took place for each hyperset across days; by daily practice, they further improved their skills for performing the particular hyperset; and 3) long-term and sequence-unselective learning that was indicated by the improvement of performance for new hypersets; the monkeys were required to learn many hypersets, each just once (a block of trials), in which they performed gradually better with more experiences in the 2 x 5 task. 3. To examine whether the memory was retained for a long period, we had the monkey learn 12 hypersets sufficiently, then we stopped the training and retested them after 1 or 6 mo. After the 1-mo interruption the performance was significantly better than that for new hypersets. After the 6-mo interruption the performance was not different from new hypersets in terms of the number of trials but was significantly better than new hypersets in terms of the performance time. The results suggest that motor memory (measured by performance time) can be retained longer than procedural memory (measured by the number of trials).     

From research to practice: the effects of the jointly sponsored dissemination of an arthritis self-care nursing intervention

Various educational programs have been developed and found to be effective in the self-management of arthritis. This study reexamined the effectiveness of one such program, "Bone Up On Arthritis" (BUOA), when the program was delivered by a community-based service organization to a sample of persons (N = 154) who differed widely in disease type and demographic characteristics. Arthritis Foundation staff implemented BUOA at four national sites; data were collected and analyzed by University of Michigan nurse researchers. Investigators found improved scores on all outcome measures (self-care behavior, helplessness, pain, dysfunction, and depression). These findings suggest that "Bone Up" is an effective nursing intervention in multiple organizational and community environments and for diverse patient populations.     

Inhibition of neuronal calcium channels by a novel peptide spider toxin, DW13.3

Peptide toxins have proved to be useful agents, both in discriminating between different components of native calcium channel currents and in the molecular isolation and designation of their cloned channel counterparts. Here, we describe the isolation and characterization of the biochemical and physiological properties of a novel 74-amino acid peptide toxin (DW13.3) extracted from the venom of the spider Filistata hibernalis. The subtype specificity of DW13.3 was investigated using calcium channel currents recorded from two separate expression systems and several different cultured mammalian cell preparations. Overall, DW13.3 potently blocked all native calcium channel currents studied, with the exception of T-type currents recorded from GH3 cells. Examination of transiently expressed calcium channels in oocytes showed that DW13.3 had the highest affinity for alpha1A, followed by alpha1B > alpha1C > alpha1E. The affinity of DW13.3 for alpha1B N-type currents varied by 10-fold between expressed channels and native currents. Although block occurred in a similar 1:1 manner for all subtypes, DW13.3 produced a partial block of both alpha1A currents and P-type currents in cerebellar Purkinje cells. Selective occlusion of the P/Q-type channel ligand omega-conotoxin MVIIC (but not omega-agatoxin IVA) from its binding site in Purkinje neurons suggests that DW13.3 binds to a site close to the pore of the channel. The inhibition of different subtypes of calcium channels by DW13.3 reflects a common "macro" binding site present on all calcium channels except T-type.     

Traffic of dynamin within individual Drosophila synaptic boutons relative to compartment-specific markers

Presynaptic terminals contain several specialized compartments, which have been described by electron microscopy. We show in an identified Drosophila neuromuscular synapse that several of these compartments-synaptic vesicle clusters, presynaptic plasma membrane, presynaptic cytosol, and axonal cytoskeleton-labeled by specific reagents may be resolved from one another by laser scanning confocal microscopy. Using a panel of compartment-specific markers and Drosophila shibire(ts1) mutants to trap an intermediate stage in synaptic vesicle recycling, we have examined the localization and redistribution of dynamin within single synaptic varicosities at the larval neuromuscular junction. Our results suggest that dynamin is not a freely diffusible molecule in resting nerve terminals; rather, it appears localized to synaptic sites by association with yet uncharacterized presynaptic components. In shi(ts1) nerve terminals depleted of synaptic vesicles, dynamin is quantitatively redistributed to the plasma membrane. It is not, however, distributed uniformly over presynaptic plasmalemma; instead, fluorescence images show "hot spots" of dynamin on the plasma membrane of vesicle-depleted nerve terminals. We suggest that these dynamin-rich domains may mark the active zones for synaptic vesicle endocytosis first described at the frog neuromuscular junction.     

The crystal structure of the immunity protein of colicin E7 suggests a possible colicin-interacting surface

The immunity protein of colicin E7 (ImmE7) can bind specifically to the DNase-type colicin E7 and inhibit its bactericidal activity. Here we report the 1.8-angstrom crystal structure of the ImmE7 protein. This is the first x-ray structure determined in the superfamily of colicin immunity proteins. The ImmE7 protein consists of four antiparallel alpha-helices, folded in a topology similar to the architecture of a four-helix bundle structure. A region rich in acidic residues is identified. This negatively charged area has the greatest variability within the family of DNase-type immunity proteins; thus, it seems likely that this area is involved in specific binding to colicin. Based on structural, genetic, and kinetic data, we suggest that all the DNase-type immunity proteins, as well as colicins, share a "homologous-structural framework" and that specific interaction between a colicin and its cognate immunity protein relies upon how well these two proteins' charged residues match on the interaction surface, thus leading to specific immunity of the colicin.     

Remote sensing of structural complexity indices for habitat and species distribution modeling

Spatial distribution models are increasingly used in ecological studies, but are limited by the poor accuracy of remote sensing (RS) for mapping microhabitat (< 0.1 ha) features. Mapping accuracy can be improved by combining advanced RS image-processing techniques with microhabitat data expressed as a structural complexity index (SCI). To test this idea, we used principal components analysis (PCA) and an additive SCI method developed for forest ecology (calculated by re-scaling and summing representative structural variables) to summarize 13 microhabitat-scale (0.04 ha) vegetation structure attributes describing the rare mountain bongo antelope's (Tragelaphus eurycerus isaaci) habitat in Kenya's Aberdare mountains. Microhabitat data were collected in 127 plots: 37 related to bongo habitat use, 90 from 1 km-spaced grid points representing overall habitat availability and bongo non-presence. We then assessed each SCI's effectiveness for discerning microhabitat variability and bongo habitat selection, using Wilcoxon Rank Sum tests for differences in mean SCI scores among plots divided into 4 vegetation classes, and the Area Under the Curve (AUC) of receiver operating characteristics from logistic regressions. We also examined the accuracy of predicted SCI scores resulting from regression models based on variables derived from a) ASTER imagery processed with spectral mixture and texture analysis, b) an SRTM DEM and c) rainfall data, using the 90 grid plots for model training and the bongo plots as an independent test dataset. Of the five SCIs derived, two performed best: the PCA-derived Canopy Structure Index (CSI) and an additive index summarizing 8 structural variables (AI₈). CSI and AI₈ showed significant differences between 5 of 6 vegetation class pairs, strong abilities to distinguish bongo-selected from available habitat (AUCs = 0.71 (CSI); 0.70 (AI₈)), and predicted scores 60-110% more accurate than reported by other studies using RS to quantify individual microhabitat structural attributes (CSI model R² = 0.51, RMSE = 0.19 (training) and 0.21 (test); AI₈ model R² = 0.46, RMSE = 0.17 (training) and 0.19 (test)). Repeating the Wilcoxon tests and logistic regressions with RS-predicted SCI values showed that AI₈ most effectively preserved the patterns found with the observed SCIs. These results demonstrate that SCIs effectively characterize microhabitat structure and selection, and boost microhabitat mapping accuracy when combined with enhanced RS image-processing techniques. This approach can improve distribution models and broaden their applicability, makes RS more relevant to applied ecology, and shows that processing field data to be more compatible with RS can improve RS-based habitat mapping accuracy.     

The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin

Glycosylated amino acids and glycosylated human serum albumin reduce nitrite to nitric oxide under anaerobic conditions. The amount of nitric oxide produced was recorded by generation of nitrosoHb from deoxyHb. Without preincubation after the addition of sodium nitrite, glucose or a mixture of glucose with amino acid or serum albumin did not cause spectrophotometrically detectible transformation of deoxyHb into nitrosoHb. The generation of NO increased with an increase in content of colored "final" products of amino acid and serum albumin glycosylation in the incubation mixture. The incubation of blood plasma of patients with diabetes mellitus with nitrite also resulted in the increased production of NO as compared to blood plasma of healthy subjects. During the incubation of healthy subjects' blood plasma with nitrite a small amount of NO was produced. The removal of low-molecular-weight compounds was accompanied by a significantly decreased generation of NO by blood plasma.