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.     

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.     

Constrained multifidelity optimization using model calibration

Multifidelity optimization approaches seek to bring higher-fidelity analyses earlier into the design process by using performance estimates from lower-fidelity models to accelerate convergence towards the optimum of a high-fidelity design problem. Current multifidelity optimization methods generally fall into two broad categories: provably convergent methods that use either the high-fidelity gradient or a high-fidelity pattern-search, and heuristic model calibration approaches, such as interpolating high-fidelity data or adding a Kriging error model to a lower-fidelity function. This paper presents a multifidelity optimization method that bridges these two ideas; our method iteratively calibrates lower-fidelity information to the high-fidelity function in order to find an optimum of the high-fidelity design problem. The algorithm developed minimizes a high-fidelity objective function subject to a high-fidelity constraint and other simple constraints. The algorithm never computes the gradient of a high-fidelity function; however, it achieves first-order optimality using sensitivity information from the calibrated low-fidelity models, which are constructed to have negligible error in a neighborhood around the solution. The method is demonstrated for aerodynamic shape optimization and shows at least an 80% reduction in the number of high-fidelity analyses compared other single-fidelity derivative-free and sequential quadratic programming methods. The method uses approximately the same number of high-fidelity analyses as a multifidelity trust-region algorithm that estimates the high-fidelity gradient using finite differences.     

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.     

Randomized controlled trial of effects of Escherichia coli antiserum on serum immunoglobulin G concentrations and morbidity and mortality rates in foals

OBJECTIVE: To determine whether administration of commercially available Escherichia coli antiserum to neonatal foals would affect serum IgG concentration or morbidity and mortality rates during the first 60 days of life. DESIGN: Randomized controlled trial. ANIMALS: 271 neonatal foals on 4 well-managed farms. PROCEDURE: Foals were randomly assigned to a treatment or control group. All foals were allowed to suckle colostrum normally. In addition, treatment-group foals were given E coli antiserum (10 micromilligrams) orally between 0 and 8 hours after birth. Serum samples were obtained between 18 and 36 hours after birth, and serum IgG concentration was determined. Foals were monitored for the first 60 days after birth, and causes of disease or death were recorded. RESULTS: Groups did not differ significantly in regard to breed, sex, month of birth, season of birth, age of dams, parity of dams, duration of gestation, or specific gravity of colostrum before suckling. In addition, groups did not differ significantly in regard to mean serum IgG concentration, prevalence of complete or partial failure of passive transfer of immunity, frequency or causes of disease, or frequency of death from infectious causes. CLINICAL IMPLICATIONS: In this group of foals on well-managed farms, administration of E coli antiserum did not alter serum IgG concentrations or morbidity and mortality rates during the first 60 days of life.     

Prevalence and predictors of sexual dysfunction in long-term survivors of marrow transplantation

PURPOSE: To describe the prevalence of sexual difficulties in men and women after marrow transplantation (MT), and to define medical, demographic, sexual, and psychologic predictors of sexual dysfunction 3 years after MT. PATIENTS AND METHODS: Four hundred seven adult MT patients were assessed pretransplantation. Survivors repeated measures of psychologic and sexual functioning at 1 and 3 years posttransplantation. RESULTS: Data were analyzed from 102 event-free 3-year survivors who defined themselves as sexually active. Men and women did not differ in sexual satisfaction pretransplantation. At 1 and 3 years posttransplantation, women reported significantly more sexual dysfunction than men. Eighty percent of women and 29% of men reported at least one sexual problem by 3 years after MT. No pretransplantation variables were significant predictors of 3-year sexual satisfaction for women. For men, pretransplantation variables of older age, poorer psychologic function, not being married, and lower sexual satisfaction predicted sexual dissatisfaction at 3 years (R2=.28; P < .001). Women who were more dissatisfied 3 years after MT did not receive hormone replacement therapy (HRT) at 1 -year posttransplantation and were less satisfied at 1 year, but not pretransplantation (R2=.35; P < .001). CONCLUSION: Sexual problems are significant in the lives of MT survivors, particularly for women. Although HRT before 1 year posttransplantation improves sexual function, it does not ensure sexual quality of life. Intervention for women is needed to apply hormonal, mechanical, and behavioral methods to prevent sexual difficulties as early after transplantation as possible.