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Predictive smooth pursuit of complex two-dimensional trajectories in monkey: component interactions.

Smooth pursuit eye movements were studied in monkeys tracking target spots that moved two-dimensionally. Complex target trajectories were created by applying either two or three sinusoids to horizontal and vertical axes in various combinations. The chance of observing predictable performance was increased by repeated training on each trajectory. Data analyses were based upon repeated presentations of each trajectory within sessions and on successive days. We wished to determine how accurately monkeys could pursue targets moving along these trajectories and to observe interactions among frequency components. At intermediate frequencies, tracking performance was smooth and consistent during repeated presentations with saccadic corrections that were well integrated with smooth pursuit. The mean gain for eight different sum-of-sines trajectories was 0.83 and the mean magnitude (absolute value) of the phase error was 6 degrees. In light of the long delays that have been associated with the processing of visual information, these values indicate that the monkeys were pursuing predictively. Five factors influenced predictive pursuit performance: (1) there was a decline in performance with increasing frequency; (2) horizontal pursuit was better than vertical pursuit; (3) high-frequency components were tracked with higher gains and phase lags, while lower-frequency components were tracked with lower gains and phase leads; (4) the gain of sinusoidal pursuit was always reduced when a second sinusoid was applied to the same axis or, to a lessor extent, when a second sinusoid of higher frequency was applied to the orthogonal axis; (5) the phase of sinusoidal pursuit shifted from a phase lag to a phase lead when combined with a second sinusoid of higher frequency, but was not affected by the addition of a lower-frequency sinusoid. Findings 1 and 2 confirm, in monkeys, results reported for humans, and 3 extends to monkeys and to two-dimensional pursuit results based upon human subjects. All of these findings demonstrate that complex predictive tracking is controlled by a nonlinear and nonhomogeneous system that uses predictive strategies in concert with feedback control to generate good pursuit.

Animals↗

Personal disruptions, social integration, subjective well-being, and predisposition toward the use of counseling services.

The importance of social integration for the subjective well-being and predisposition toward professional counseling services of persons experiencing personal disruptions is explored among 1,423 northwest Wisconsin residents. Considerable support is found for the hypothesis that greater contact with close friends diminishes the effect of personal disruptions (health problems, marital break-up, and unemployment) on individual well-being. Some evidence is found in favor of the proposition that greater contact with close friends for those with disruptions reduces the inclination to use professional counselors. And, unexpectedly, the frequency of interaction with friends for those without stressful events is not found to significantly influence the level of morale. Friendship ties and counseling services are suggested as alternative resources for persons in crisis, and the relevance of findings on social integration, personal disruptions, and morale for models of subjective well-being is discussed.

Adult↗

Concurrent transfer and recombination between plasmids encoding for heat-stable enterotoxin and drug resistance in porcine enterotoxigenic Escherichia coli.

The frequency of and genetic mechanisms for simultaneous transfer of genes encoding for tetracycline and sulpha-streptomycin resistance, heat-labile (LT) and heat-stable (ST-mouse) enterotoxin production in porcine enterotoxigenic Escherichia coli to Escherichia coli K12 were investigated. Seven E. coli strains of 0-group 149 were studied by conjugation and transformation experiments. All strains transferred tetracycline-resistance plasmids at a high frequency. No interaction was observed between these plasmids and those encoding for LT production. However, most tetracycline-resistant recipient cells were ST-mouse+ following recombination events between plasmids encoding for colicin B and ST-mouse production and plasmids encoding for tetracycline resistance. Alternatively, when selecting for sulpha or streptomycin resistance a majority of the transconjugants were also ST-mouse+, as plasmids coding for sulpha and streptomycin were mobilized by the colicin B and ST-mouse encoding plasmid. Since the simultaneous transfer of genes encoding for drug resistance, colicin B and ST-mouse production are common events in vitro, they might also occur frequently in vivo during antibiotic selective pressure.

Animals↗

Effect of G-6 PD deficiency on sickle cell disease in Saudi Arabia.

High incidence of G6PD deficiency has been reported in areas of the eastern province of Saudi Arabia where sickle cell gene is also prevalent. This study was conducted to assess the co-incidence of this enzymopathy with Hb S and its influence upon the clinical and hematological expression of sickle cell disease. Eighty three children with SS disease, 145 patients with sickle cell trait and 100 random cord blood as samples with normal Hb AF, and an FS electrophoretic pattern respectively were examined. The frequency of interaction of G6PD deficiency with Hb S was found significantly increased but no effect of this enzyme defect was discerned on the clinical and hematological status of homozygous sickle cell disease.

Anemia, Sickle Cell↗

A consistent potential energy parameter set for lipids: dipalmitoylphosphatidylcholine as a benchmark of the GROMOS96 45A3 force field.

The performance of the GROMOS96 parameter set 45A3 developed for aliphatic alkanes is tested on a bilayer of dipalmitoylphosphatidylcholine (DPPC) in water in the liquid-crystalline L(alpha) phase. Variants of the force-field parameter set as well as different sets of simulation conditions or simulation parameter sets are evaluated. In the case of the force-field parameters, the van der Waals constants for the non-bonded interaction of the ester carbonyl carbon and the partial charges and charge group definition of the phosphatidylcholine head group are examined. On the methodological side, different cut-off distances for the non-bonded interactions, use of a reaction-field force due to long-range electrostatic interactions, the frequency of removal of the centre of mass motion and the strength of the coupling of the pressure of the system to the pressure bath are tested. The area per lipid, as a measure of structure, the order parameters of the chain carbons, as a measure of membrane fluidity, and the translational diffusion of the lipids in the plane of the bilayer are calculated and compared with experimental values. An optimal set of simulation parameters for which the GROMOS96 parameter set 45A3 yields a head group area, chain order parameters and a lateral diffusion coefficient in accordance with the experimental data is listed.

1,2-Dipalmitoylphosphatidylcholine↗

A linear canal-otolith interaction model to describe the human vestibulo-ocular reflex.

A control systems model of the vestibulo-ocular reflex (VOR) originally derived for yaw rotation about an eccentric axis (Crane et al. 1997) was applied to data collected during ambulation and dynamic posturography. The model incorporates a linear summation of an otolith response due to head translation scaled by target distance, adding to a semi-circular canal response that depends only on angular head rotation. The results of the model were compared with human experimental data by supplying head angular velocity as determined by magnetic search coil recording as the input for the canal branch of the model and supplying linear acceleration as determined by flux gate magnetometer measurements of otolith position. The model was fit to data by determining otolith weighting that enabled the model to best fit the data. We fit to the model experimental data from normal subjects who were: standing quietly, walking, running, or making active sinusoidal head movements. We also fit data obtained during dynamic posturography tasks of: standing on a platform sliding in a horizontal plane at 0.2 Hz, standing directly on a platform tilting at 0.1 Hz, and standing on the tilting platform buffered by a 5-cm thick foam rubber cushion. Each task was done with the subject attending a target approximately 500, 100, or 50 cm distant, both in light and darkness. The model accurately predicted the observed VOR response during each test. Greater otolith weighting was required for near targets for nearly all activities, consistent with weights for the otolith component found in previous studies employing imposed rotations. The only exceptions were for vertical axis motion during standing, sliding, and tilting when the platform was buffered with foam rubber. In the horizontal axis, the model always fit near target data better with a higher otolith component. Otolith weights were similar with the target visible and in darkness. The model predicts eye movement during both passive whole-body rotation and free head movement in space implying that the VOR is controlled by a similar mechanism during both situations. Factors such as vision, proprioception, and efference copy that are available during head free motion but not during whole-body rotation are probably not important to gaze stabilization during ambulation and postural stabilizing movement. The linearity of the canal-otolith interaction was tested by re-analysis of the whole body rotation data on which the model is based (Crane et al. 1997). Normalized otolith-mediated gain enhancement was determined for each axis of rotation. This analysis uncovered minor non-linearities in the canal-otolith interaction at frequencies above 1.6 Hz and when the axis of rotation was posterior to the head.

Adult↗

Genetics and adaptation in structured populations: sex ratio evolution in Silene vulgaris.

Theoretical models suggest that population structure can interact with frequency dependent selection to affect fitness in such a way that adaptation is dependent not only on the genotype of an individual and the genotypes with which it co-occurs within populations (demes), but also the distribution of genotypes among populations. A canonical example is the evolution of altruistic behavior, where the costs and benefits of cooperation depend on the local frequency of other altruists, and can vary from one population to another. Here we review research on sex ratio evolution that we have conducted over the past several years on the gynodioecious herb Silene vulgaris in which we combine studies of negative frequency dependent fitness on female phenotypes with studies of the population structure of cytoplasmic genes affecting sex expression. This is presented as a contrast to a hypothetical example of selection on similar genotypes and phenotypes, but in the absence of population structure. Sex ratio evolution in Silene vulgaris provides one of the clearest examples of how selection occurs at multiple levels and how population structure, per se, can influence adaptive evolution.

Adaptation, Biological↗

Possible factors leading to a misjudgement of mutant frequencies in HPRT assay.

Interactions between cloning efficiency (CE) and mutant frequency (MF) in the HPRT clonal assay in in vitro study were analysed. In 12 separate reconstruction experiments with independent pairs of wild type (WT) and mutant (HPRT-) clones, the CE of WT cells (Group 1) and the recovery of mutant cells in absence (Group 2), as well as in the presence of non-irradiated (Group 3), or irradiated (Group 4) WT cells (10(4) cells/well) was determined. The plating of mutant cells with irradiated WT cells improved their CEs by almost 30%. In contrast, the presence of non-irradiated WT cells led to a slight decline (10%) in CE of mutant cells, resulting in a significant difference between groups (p = 0.0083). The extent of decline in survival of mutant cells in the presence of non-irradiated WT cells negatively correlated (r = 0.3496, p < 0.05) with the initial CE of WT cells. The data suggest that the presence of WT cells in the selection plates may suppress the recovery of mutants in HPRT assay, and this negative effect is stronger in samples with high CE. These findings indicate a possible source for a serious underestimation of mutant frequencies (3-fold in the range of CEs from 10% to 60%) in the HPRT assay and may be useful for the interpretation of results from studies on exposure to mutagens in humans.

Humans↗

Mechanism of allergic cross-reactions--I. Multispecific binding of ligands to a mouse monoclonal anti-DNP IgE antibody.

A recently developed solid-phase binding assay was used to investigate the specificity of ligand binding to a mouse monoclonal anti-dinitrophenyl IgE [IgE(aDNP)]. All DNP-amino acids, that were tested, inhibited the binding of radio-labeled IgE(aDNP) to DNP covalently attached to polystyrene microtiter plates; however, the concentration for 50% inhibition varied within four orders of magnitude, DNP-L-serine being the most, DNP-proline the least potent inhibitor. In addition to DNP analogues a large number (2074) of drugs and other compounds were tested for their ability to compete with DNP for the binding site of IgE(aDNP). At the concentrations used for screening 59% of the compounds had no significant inhibition; 19% inhibited the binding of IgE(aDNP) more than 50%. Several families of compounds (tetracyclines, polymyxines, phenotiazines, salicylates and quinones) of effective competitors were found. Within these families change in the functional groups attached to the "family stem" had major effects on the affinity of ligand binding. The occurrence frequencies of interactions of ligands with IgE(aDNP) is in good agreement with a semi-empirical model for multispecific antibody-ligand interactions.

Amino Acids↗

Assessment of the repair and damage of DNA induced by parent and reduced RSU-1069, a 2-nitroimidazole-aziridine.

The cellular repair and damage of DNA induced by parent and reduced RSU-1069, a 2-nitroimidazole-aziridine, was assessed at both the molecular and cellular level. At the molecular level, after in vitro incubation with parent or reduced RSU-1069, plasmid DNA was transfected into Escherichia coli (AB1157) with subsequent selection for gene expression. For equivalent levels of DNA strand breakage following such treatment it is evident from the relative transformation frequencies that interactions with reduced RSU-1069 lead to DNA damage consistent with bifunctional action of a metabolite(s). At the cellular level, the cytoxicity of RSU-1069 was determined for a series of repair deficient mutants of E. coli under both aerobic and hypoxic conditions. The differential aerobic:hypoxic cytotoxicity ratio is approximately 3. We conclude that the repair of cellular DNA damage induced by RSU-1069 involves activation of the gene products under the control of the recA gene and not those under the control of the ada gene. The ability of cellular systems to repair damage induced by RSU-1069 may play a significant role in determining its efficiency to act as a hypoxic cell radiosensitizer and a hypoxia selective cytotoxin.

Aerobiosis↗

Anxiety sensitivity interacts with marijuana use in the prediction of anxiety symptoms and panic-related catastrophic thinking among daily tobacco users.

The present investigation evaluated whether anxiety sensitivity interacted with marijuana use in relation to the prediction of panic-relevant variables among young adult tobacco smokers (n=265). Approximately 73% of the sample was composed of current marijuana smokers, with 78.5% of this sub-sample using marijuana more than once per week. As expected, after covarying cigarettes per day, alcohol use, and negative affectivity, the interaction between marijuana use and anxiety sensitivity predicted anxiety symptoms and agoraphobic cognitions. Partially consistent with prediction, the interaction between frequency of marijuana use and anxiety sensitivity predicted only anxiety symptoms. These results are discussed in relation to better understanding the potential role of regular marijuana use and anxiety sensitivity for panic-relevant emotional vulnerability among regular tobacco smokers.

Adolescent↗

Rapid versus non-rapid cycling as a predictor of response to olanzapine and divalproex sodium for bipolar mania and maintenance of remission: post hoc analyses of 47-week data.

BACKGROUND: Rapid cycling in bipolar disorder has been associated with greater morbidity. We examine whether rapid cycling affects treatment response to olanzapine or divalproex in acute mania. METHODS: A post hoc analysis of a 47-week, randomized, double-blind study compared olanzapine (5-20 mg/day) to divalproex sodium (500-2500 mg/day) for bipolar manic or mixed episodes (N=251). Young Mania Rating Scale (YMRS) scores > or = 20 were required for inclusion. Patients were classified at study entry as "rapid cyclers" if they experienced > or = 4 episodes within the last year. A repeated measures analysis of variance was used to analyze YMRS change from baseline. RESULTS: A significant three-way interaction (cycling frequency by medication by visit) was found when modeling change in YMRS total scores. For patients with bipolar I disorder identified as rapid cyclers, mania improvement across the trial did not differ significantly between treatment groups (p=0.181). Among non-rapid cyclers, olanzapine-treated patients had significantly greater YMRS improvement than divalproex-treated patients across the trial (p<0.001) and at most time points. Among olanzapine-treated patients, non-rapid cyclers experienced numerically greater YMRS improvement than rapid cyclers throughout the trial; statistically significant differences occurred at weeks 11, 15 and 39. In contrast, among divalproex-treated patients, YMRS scores were significantly better in rapid cyclers than non-rapid cyclers during the first two study weeks but were comparable thereafter. A similar pattern was seen in Clinical Global Impressions-Mania Severity scores. Hamilton Depression scores in rapid versus non-rapid cycling patients differed at some time points but not over the entire trial and differences by cycling status were not treatment-specific. LIMITATIONS: Apart from the post hoc nature of the analyses, there were high dropout rates in both groups, and cycle frequency was not taken into account. CONCLUSIONS: Rapid cycling patients did less well over long-term treatment than non-rapid cycling patients. Among rapid cycling patients, olanzapine and divalproex appear similarly effective against manic symptoms; however, among non-rapid cycling patients, olanzapine-treated patients experienced superior mania improvement. Olanzapine-treated, non-rapid cyclers experienced greater mania improvement than rapid cyclers. The converse was true of divalproex-treated patients early in treatment.

Adult↗

The impact of lexical-semantic impairment and of executive dysfunction on the word reading performance of patients with probable Alzheimer dementia.

The influence of lexical-semantic impairment and of executive dysfunction on word naming performance was investigated in a group of patients with probable Alzheimer dementia (AD). The patients, who varied in the severity of the illness, were tested in a word naming task where they had to read aloud Italian three-syllable words with a dominant or subordinate stress pattern. These types of words have been shown to interact with frequency in normal adults [J. Exp. Psychol.: Hum. Percept. Perform. 18 (4) (1992) 987], so that the effect of the subordinate stress pattern (slower reading times) is only apparent for low frequency words. The frequency and stress effects on accuracy increased across dementia severity levels. Regression analyses showed that the impairment in reading low frequency words with subordinate stress depended largely on the level of lexical-semantic impairment, measured by a test of semantic memory and comprehension. Implications for the current reading models are discussed.

Aged↗

The dynamics of natural killer cell tolerance.

Natural killer (NK) cells are important mediators of resistance against tumor growth and metastasis. NK cell reactivity is regulated by a balance of signals from activating and inhibitory receptors. While reactivity against tumor cells is beneficial, it is essential that NK cells do not attack normal tissue. The distinction between tumor cells and normal cells is partly made at the level of activating receptors: transformation often results in induction of ligands for such receptors. In addition, NK cells discriminate self from non-self using MHC class I-binding inhibitory receptors. Host MHC class I molecules regulate development of NK cell reactivity and tolerance, a process that is not well understood. Recent data suggest that functional maturation may not be a binary phenomenon: quantitative aspects, with regards to avidity and frequency in interactions between developing NK cells and normal cells, may be important for the generation of NK cells that are 'tuned' to optimally sensing the absence of self-MHC class I. In this article, we discuss models for development of NK cell reactivity and tolerance. Our understanding of this process may have significant implications for the use of NK cells in cancer therapy.

Animals↗

Sequential decision-making in a variable environment: modeling elk movement in Yellowstone National Park as a dynamic game.

We develop a suite of models with varying complexity to predict elk movement behavior during the winter on the Northern Range of Yellowstone National Park (YNP). The models range from a simple representation of optimal patch choice to a dynamic game, and we show how the underlying theory in each is related by the presence or absence of state- and frequency-dependence. We compare predictions from each of the models for three variables that are of basic and applied interest: elk survival, aggregation, and use of habitat outside YNP. Our results suggest that despite low overall forage depletion in the winter, frequency-dependence is crucial to the predictions for elk movement and distribution. Furthermore, frequency-dependence interacts with mass-dependence in the predicted outcome of elk decision-making. We use these results to show how models that treat single movement decisions in isolation from the seasonal sequence of decisions are insufficient to capture landscape scale behavior.

Animal Migration↗

Contrasts in social structure among black-and-white colobus monkey groups.

Three types of Colobus guereza groups may be distinguished on the bases of size and composition, namely small one-male groups, large, one-male groups and multi-male groups. The social structure of each type of group is described in terms of the distribution of non-agonistic interactions, the frequency and distribution of agonistic behaviour and the organization of the roles of vigilance, territorial defence and leadership. A number of differences are found between the group types which appear to be related to the differences in group size and composition. It is suggested that these group types represent stages in the life-cycle of colobus groups, and that such an interpretation may help to resolve some of the conflicting reports in the literature.

Agonistic Behavior↗

Induction of proliferation and cytokine production in human T lymphocytes by lipopolysaccharide (LPS).

Lipopolysaccharide (LPS), also known as endotoxin, is a compound of the cell wall of Gram-negative bacteria, which has been demonstrated to induce inflammatory reactions in vitro as well as in vivo, including lethal shock. A great number of different cells have been documented to be reactive to LPS, e.g. monocytes/macrophages, vascular cells, polymorphonuclear cells, and even B lymphocytes. We have now established that T lymphocytes could also contribute to an inflammatory reaction to LPS. LPS is a potent inducer of human T-lymphocyte proliferation and cytokine production. The activation of T lymphocytes by LPS requires direct cell-to-cell contact with viable accessory monocytes. This interaction was found to be MHC-unrestricted, but strongly dependent on costimulatory signals provided by B7/CD28 interactions. The frequency of responding T lymphocytes is less than 1:1000. A very exciting finding was that not only monocytes, but also CD34+ hematopoietic stem cells, which circulate in peripheral blood in very low frequency, exert essential accessory cell activity during stimulation of T lymphocytes by LPS. In contrast, the response of T lymphocytes to conventional recall antigens is not controlled by blood stem cells. These conclusions are based on the observation that depletion of CD34-positive blood stem cells resulted in a complete loss of LPS-induced T-lymphocyte stimulation. Addition of CD34-enriched blood stem cells led to a recovery of reactivity of T lymphocyte to LPS. The characteristics of T-lymphocyte activation indicate that LPS is neither active as a mitogen, or as a superantigen, or as a classical antigen, but may activate T lymphocyte through a new, so far undescribed, mechanism. Furthermore, the involvement of hematopoietic blood stem cells in the activation of T lymphocytes by LPS demonstrates a role of these cells in inflammatory and immunological events.

Animals↗