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PubMed2004

High-throughput mutation detection underlying adaptive evolution of Escherichia coli-K12.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis of base-specific cleavage products is an efficient, highly accurate tool for the detection of single base sequence variations. We describe the first application of this comparative sequencing strategy for automated high-throughput mutation detection in microbial genomes. The method was applied to identify DNA sequence changes that occurred in Escherichia coli K-12 MG1655 during laboratory adaptive evolution to new optimal growth phenotypes. Experiments were based on a genome-scale in silico model of E. coli metabolism and growth. This model computes several phenotypic functions and predicts optimal growth rates. To identify mutations underlying a 40-d adaptive laboratory evolution on glycerol, we resequenced 4.4% of the E. coli-K12 MG1655 genome in several clones picked at the end of the evolutionary process. The 1.54-Mb screen was completed in 13.5 h. This resequencing study is the largest reported by MALDI-TOF mass spectrometry to date. Ten mutations in 40 clones and three deviations from the reference sequence were detected. Mutations were predominantly found within the glycerol kinase gene. Functional characterization of the most prominent mutation shows its metabolic impact on the process of adaptive evolution. All sequence changes were independently confirmed by genotyping and Sanger-sequencing. We demonstrate that comparative sequencing by base-specific cleavage and MALDI-TOF mass spectrometry is an automated, fast, and highly accurate alternative to capillary sequencing.

Adaptation, Biological↗
PubMed2004

Impact on couple relationships of predictive testing for Huntington disease: a longitudinal study.

Since predictive testing has been available for Huntington disease (HD) and similar adult-onset neurodegenerative disorders, research into the psychosocial impact of test results has focussed on those receiving results, and to a lesser extent, on their partners. Few studies have examined the impact of predictive testing on the couple relationship, particularly from the perspective of family systems theory. This longitudinal study compared the level of marital adjustment of 23 couples in which the at-risk partner is undergoing predictive testing for HD (the testing group) with that of 20 couples in which the at-risk partner is not undergoing testing (the non-testing group). Participating couples completed a relationship measure, the Dyadic Adjustment Scale, at baseline and on two subsequent occasions. Using non-parametric tests, comparisons were made at each phase between the couple scores of the testing and non-testing groups but no significant differences were found in the levels of marital adjustment. Within the testing group the same comparisons were made for the carrier and non-carrier subgroups, and a significant difference was found at the final phase. There was an increase in the level of marital adjustment for the carrier group and a decrease for the non-carrier group. Together with trends observed in the data, this finding suggests a need for greater attention to be given to the potential impact of predictive testing on the couple relationship. Offering couples pre-result relationship assessment and referral for couple therapy, if warranted, may enhance the quality of professional support during the predictive testing process.

Adaptation, Psychological↗
PubMed1993

An adaptive finite-element approach for the analysis of dental restorations.

The present paper deals with the problem of stresses generated during the setting process of polymer tooth fillings. A finite element procedure capable of accurately predicting the stresses along an interface between two different materials is presented. Adaptation of the finite element mesh is carried out based on a simple error estimator. The procedure is tested against benchmark problems and then applied to polymer tooth fillings. The results of the study are relevant in understanding and improving the behaviour of dental restorations.

Dental Cavity Preparation↗
PubMed1985

Site of impulse initiation in tendon organs of cat soleus muscle.

A continuing controversy surrounds the question of whether Golgi tendon organs are examples of receptors in which impulses may be generated at more than one site. This paper reports a systematic examination of a number of models incorporating single or multiple impulse generators and of the compatibility of their predictions with experimental observations. Two phenomena, in particular, that must be accounted for are nonlinear summation and cross-adaptation. When two motor units each with a direct effect on the tendon organ are stimulated together, the rate of discharge is greater than either individual rate but is less than their sum. In cross-adaptation a conditioning response elicited by one motor unit contraction produces adaptation of the discharge associated with stimulation of a second motor unit. A model with a central impulse generator can be modified to account for nonlinear summation by postulating a nonlinear transformation in the generator current-to-impulse rate conversion. Experiments measuring summation of responses to stimulation of three inputs produced results that did not support this model. Another variation of the model, which had a nonlinearity in the tension-to-current step and cross-connections (mechanical or neural) between tendon strands stressed by contracting muscle fibers, was able to account for the observations. A second model that provided the right predictions was a multiple impulse generator with cross-connections. Which of the two models best fits the experimental observations can be decided by comparing the calculated summation coefficients and cross-adaptation coefficients. A central impulse generator predicts a negative correlation, the multiple impulse generator a positive correlation. All of the observations were made using tendon organs of cat soleus muscle. Responses were recorded to stimulation of filaments of ventral root. In a comparison between 20 pairs of responses from six tendon organs the correlation between summation and cross-adaptation coefficients was found to be significantly positive. We conclude that the tendon organ model that accurately predicts all of the experimental observations incorporates multiple generators.

Adaptation, Physiological↗
PubMed2005

Kv7/KCNQ/M and HCN/h, but not KCa2/SK channels, contribute to the somatic medium after-hyperpolarization and excitability control in CA1 hippocampal pyramidal cells.

In hippocampal pyramidal cells, a single action potential (AP) or a burst of APs is followed by a medium afterhyperpolarization (mAHP, lasting approximately 0.1 s). The currents underlying the mAHP are considered to regulate excitability and cause early spike frequency adaptation, thus dampening the response to sustained excitatory input relative to responses to abrupt excitation. The mAHP was originally suggested to be primarily caused by M-channels (at depolarized potentials) and h-channels (at more negative potentials), but not SK channels. In recent reports, however, the mAHP was suggested to be generated mainly by SK channels or only by h-channels. We have now re-examined the mechanisms underlying the mAHP and early spike frequency adaptation in CA1 pyramidal cells by using sharp electrode and whole-cell recording in rat hippocampal slices. The specific M-channel blocker XE991 (10 microm) suppressed the mAHP following 1-5 APs evoked by current injection at -60 mV. XE991 also enhanced the excitability of the cell, i.e. increased the number of APs evoked by a constant depolarizing current pulse, reduced their rate of adaptation, enhanced the after depolarization and promoted bursting. Conversely, the M-channel opener retigabine reduced excitability. The h-channel blocker ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride; 10 microm) fully suppressed the mAHP at -80 mV, but had little effect at -60 mV, whereas XE991 did not measurably affect the mAHP at -80 mV. Likewise, ZD7288 had little or no effect on excitability or adaptation during current pulses injected from -60 mV, but changed the initial discharge during depolarizing pulses injected from -80 mV. In contrast to previous reports, we found that blockade of Ca2+-activated K+ channels of the SK/KCa type by apamin (100-400 nm) failed to affect the mAHP or adaptation. A computational model of a CA1 pyramidal cell predicted that M- and h-channels will generate mAHPs in a voltage-dependent manner, as indicated by the experiments. We conclude that M- and h-channels generate the somatic mAHP in hippocampal pyramidal cells, with little or no net contribution from SK channels.

Action Potentials↗
PubMed2025

Compensatory evolution to DNA replication stress is robust to nutrient availability.

Evolutionary repair refers to the compensatory evolution that follows perturbations in cellular processes. While evolutionary trajectories are often reproducible, other studies suggest they are shaped by genotype-by-environment (GxE) interactions. Here, we test the predictability of evolutionary repair in response to DNA replication stress-a severe perturbation impairing the conserved mechanisms of DNA synthesis, resulting in genetic instability. We conducted high-throughput experimental evolution on Saccharomyces cerevisiae experiencing constitutive replication stress, grown under different glucose availability. We found that glucose levels impact the physiology and adaptation rate of replication stress mutants. However, the genetics of adaptation show remarkable robustness across environments. Recurrent mutations collectively recapitulated the fitness of evolved lines and are advantageous across macronutrient availability. We also identified a novel role of the mediator complex of RNA polymerase II in adaptation to replicative stress. Our results highlight the robustness and predictability of evolutionary repair mechanisms to DNA replication stress and provide new insights into the evolutionary aspects of genome stability, with potential implications for understanding cancer development.

DNA Replication↗
PubMed1991

The dawn of Darwinian medicine.

While evolution by natural selection has long been a foundation for biomedical science, it has recently gained new power to explain many aspects of disease. This progress results largely from the disciplined application of what has been called the adaptations program. We show that this increasingly significant research paradigm can predict otherwise unsuspected facets of human biology, and that it provides new insights into the causes of medical disorders, such as those discussed below: 1. Infection. Signs and symptoms of the host-parasite contest can be categorized according to whether they represent adaptations or costs for host or parasite. Some host adaptations may have contributed to fitness in the Stone Age but are obsolete today. Others, such as fever and iron sequestration, have been incorrectly considered harmful. Pathogens, with their large populations and many generations in a single host, can evolve very rapidly. Acquisition of resistance to antibiotics is one example. Another is the recently demonstrated tendency to change virulence levels in predictable ways in response to changed conditions imposed incidentally by human activities. 2. Injuries and toxins. Mechanical injuries or stressful wear and tear are conceptually simpler than infectious diseases because they are not contests between conflicting interests. Plant-herbivore contests may often underlie chemical injury from the defensive secondary compounds of plant tissues. Nausea in pregnancy, and allergy, may be adaptations against such toxins. 3. Genetic factors. Common genetic diseases often result from genes maintained by other beneficial effects in historically normal environments. The diseases of aging are especially likely to be associated with early benefits. 4. Abnormal environments. Human biology is designed for Stone Age conditions. Modern environments may cause many diseases-for example, deficiency syndromes such as scurvy and rickets, the effects of excess consumption of normally scarce nutrients such as fat and salt, developmental diseases such as myopia, and psychological reactions to novel environments. The substantial benefits of evolutionary studies of disease will be realized only if they become central to medical curricula, an advance that may at first require the establishment of one or more research centers dedicated to the further development of Darwinian medicine.

Adaptation, Physiological↗
PubMed2001

Adaptive filtering in exercise high resolution ECG as applied to the hypertrophic cardiomyopathy.

The application of adaptive filtering to ECG signals has been investigated for many years. This study shows that the exercise high resolution ECG (HRECG) can also be processed successfully in a similar way. Two groups were included consisting of 20 healthy individuals and 24 patients with hypertrophic cardiomyopathy (HCM). The HRECG parameters for both groups were similar (QRSdur: 107 +/- 7 vs 114 +/- 18 ms NS, LAS: 25 +/- 8 vs 22 +/- 6 ms NS). In the first step, the HRECG signal was acquired at rest to obtain the averaged reference pattern. The next step was associated with peak exercise in which one could calculate short duration averaging (approximately 30 beats) or apply adaptive filtering in which the exercise component (EC) was extracted. Exercise was performed in the supine position on a bicycle ergometer. The load of 50 W was incremented by 50-W steps in 3-minute intervals and the test was ended by fatigue. Signals were recorded in X, Y, and Z bipolar leads with a 20-Hz high pass filter. The short time average QRS duration mostly was abbreviated in normal individuals in contrast to HCM patients in which ventricular activity prolonged with sensitivity, specificity, and negative and positive predictive values: 79%, 65%, 73%, and 72%, respectively. The adaptive recurrent filtration (ARF) after cutoff of the EC at the level of 70 ms (this level is the EC mean value of both groups) showed the following statistics: 63%, 90%, 88%, and 90%. The Student's t-test as applied to the duration of EC allowed a statistically significant difference between normals and HCM patients (66 +/- 4 vs 71 +/- 6 ms, P < 0.0052) and between HCM patients with and without ventricular tachyarrhythmia and DS (74 +/- 6 vs 69 +/- 6 ms, P < 0.046).

Artifacts↗
PubMed2001

Comparison of the 5' leader sequences of North American isolates of reference and field strains of porcine reproductive and respiratory syndrome virus (PRRSV).

The 5' leader is documented to be an important regulatory element in many (+) ssRNAvirus genome. To understand the significance of the 5' leader RNA of PRRSV, we determined the complete leader sequences of fifteen different North American strains of PRRSV and predicted their secondary structures. Viruses analysed included three reference strains and nine field strains originating from different geographic locations. To further examine the leader region, one of the field strains was adapted to grow in tissue culture, and three clones were isolated. We also predicted the secondary structures of two European strains based on their published sequences. The predicted RNA secondary structures of the leader sequences suggested the existence of three conserved domains formed by the 5' region of the leader among the North American strains, two of which were conserved in the European strains. A variable structural domain was predicted from the 3' region of the leader sequences of the North American strains, where all tissue culture-adapted isolates were characterized by a stem-loop while field isolates were characterized by an internal bulge within the stem-loop.

5' Untranslated Regions↗
PubMedDate not supplied

NCLEX-RN performance: predicting success on the computerized examination.

Since the adoption of the Computerized Adaptive Testing (CAT) format of the National Certification Licensure Examination for Registered Nurses (NCLEX-RN), no studies have been reported in the literature on predictors of successful performance by baccalaureate nursing graduates on the licensure examination. In this study, a discriminant analysis was used to identify which of 21 variables can be significant predictors of success on the CAT NCLEX-RN. The convenience sample consisted of 289 individuals who graduated from a baccalaureate nursing program between 1995 and 1998. Seven significant predictor variables were identified. The total number of C+ or lower grades earned in nursing theory courses was the best predictor, followed by grades in several individual nursing courses. More than 93 per cent of graduates were correctly classified. Ninety-four per cent of NCLEX "passes" were correctly classified, as were 92 per cent of NCLEX failures. This degree of accuracy in classifying CAT NCLEX-RN failures represents a marked improvement over results reported in previous studies of licensure examinations, and suggests the discriminant function will be helpful in identifying future students in danger of failure. J Prof Nurs 17:158-165, 2001.

Adult↗
PubMed1997

Cross-cultural patterns and the search for evolved psychological mechanisms.

Darwin's principle of evolution by natural selection provides a theoretical basis for functional analyses of behaviour. This approach is complementary to traditional psychology: ideas about what behaviour was designed to do suggest how it might be organized. The cross-cultural record, because it focuses on the broadest characterization of human behaviour, can guide our search for psychological adaptations. Both universals (behavioural traits that are invariantly expressed despite cultural diversity) and conditional universals (behaviours that vary predictably with some environmental parameter) deserve attention from evolutionary psychologists. These behaviours are not themselves adaptations but are markers for underlying psychological traits that have been favoured by selection because they produce adaptive behavioural output. One universal (reciprocity) and one conditional universal (matrilineal investment bias) are used to exemplify how behavioural universals can guide the search for psychological adaptations.

Adaptation, Psychological↗
PubMed2003

Sequence, time, or state representation: how does the motor control system adapt to variable environments?

Does the observation of well-timed movements imply the existence of some internal representation of time, such as a hypothetical neural clock? Here we report the results of experiments designed to investigate whether subjects form a correct adaptive representation of mechanical environments that change in a very predictable manner. In these experiments, subjects were asked to execute arm movements over a two-dimensional workspace while experiencing time-dependent disturbing forces. We provide a formal definition for time representation and conclude that our subjects didn't use time representation for motor adaptation under the tested conditions. Subjects performed arm-reaching movements in the following experiments: (1) six experiments in a sinusoidal time-varying force field; (2) six experiments in a simple sequence of alternating viscous force fields, in which the number of targets allowed for the approximation of the force by a complex state-dependent force field; and (3) six experiments in the same simple sequence of alternating viscous force fields, in which no state-dependent force field approximation was possible. We found that the subjects did not adapt to the time-varying force field and were unable to form an adequate representation of the simple sequence of force fields. In the latter case, whenever possible, they adapted to a single state-dependent field that produced forces similar to the two alternating fields. This state-dependent field produced the same forces as the applied sequence of fields only over the trajectories that subjects executed during the training phase. However, the state-dependent field was inadequate to produce the correct forces generated by the field sequence over a new set of trajectories.These results are not consistent with the hypothesis that subjects would develop a correct representation of time-dependent forces, at least under the tested circumstances. We speculate that the system responsible for adaptation of movements to external forces may be unable to employ temporal representation. While it is possible that such a representation may emerge in a more prolonged and/or intense training, our findings indicate a preference by the adaptive system to generalize based on representing dependence of external forces upon state rather than upon time.

Adaptation, Physiological↗
PubMed2025

Adaptation of the Cyst Nematode Globodera pallida to the Colinear Potato Resistant QTLs GpaVvrn and GpaVspl Involved Distinct Genomic Regions and Absence of Cross-Virulence.

The use of alternative methods to control cyst nematode populations has accelerated since the ban of chemical nematicides in Europe. The resistant QTL GpaVvrn, derived from the wild species Solanum vernei, is widely present in resistant European potato cultivars and provides strong protection against Globodera pallida populations although a risk of resistance breakdown has already been demonstrated in both experimental evolution studies and field populations. The wild relative S. sparsipilum, harbouring the resistant QTL GpaVspl, would be an interesting alternative source of resistance to control virulent G. pallida. The goal of the present study was to understand the genomics of adaptation of the nematode to these two colinear resistant QTLs. Starting with two natural populations, an experimental evolution approach allowed, after 10 generations on resistant potato genotypes, selecting independent nematode lineages adapted to each QTL. These virulent lineages were analysed through a combination of phenotyping and genome scans approaches. Phenotyping enabled the quantification of virulence levels and confirmed resistance breakdowns. Pool-Seq whole genome sequencing followed by genome scan analyses identified genomic regions under selection, potentially involved in the adaptive mechanisms to each resistance factor. Candidate genes within these regions provided insights into the genetic basis of adaptation, revealing effectors known to suppress plant immunity. As genome scans highlighted distinct genomic regions for the adaptation to both resistant factors, we were able to predict and phenotypically confirm the absence of cross-virulence between nematode lineages evolving on GpaVvrn and GpaVspl. These findings have significant implications for the design of effective and sustainable resistance management strategies.

Animals↗
PubMed1997

Bandura's theory of self-efficacy: applications to oncology.

Self-efficacy (Bandura, 1986) has been shown to impact on health practices as well as adaptation to illness and treatment. The purposes of this paper are to describe self-efficacy theory and review literature using self-efficacy theory to investigate prevention of cancer and adaptation to cancer. Measurement of self-efficacy is also discussed. Evidence from research examining applications of Bandura's theory of self-efficacy in oncology suggests relationships between self-efficacy and cancer prevention and self-efficacy and adaptation to cancer. Strong percepts of self-efficacy predict intention to quit smoking, increased participation in screening programs, and adjustment to cancer diagnosis. Increased self-efficacy is associated with increased adherence to treatment, increased self-care behaviors, and decreased physical and psychological symptoms. The advanced practice nurse is in an excellent position to give feedback that may help support patients' self-efficacy.

Adaptation, Psychological↗
PubMed1984

Characterization and prediction of lithium blood levels and clearances.

Mathematical simulations and nonlinear numerical methods for characterizing the serum elimination half-life, volume of distribution, and renal clearance of lithium after multiple oral doses of lithium carbonate and two or more blood level determinations were constructed and adapted for clinical use. These characteristics were measured for 24 inpatients; predictions were made with the simulation and compared with actual succeeding blood levels. The average elimination half-life of 25.9 hours was compared with half-lives reported after single oral doses. Average and median errors of prediction were negligible; the root mean square error was 0.12 mEq/L, near the coefficient of variation of 0.082 mEq/L. The correlation between predicted and observed levels (r) was .82; a small systematic effect of weight was found.

Administration, Oral↗
PubMed1986

Some tests of the Marr-Ullman model of movement detection.

Several psychophysical experiments are described which test and uphold predictions derived from the Marr-Ullman model of movement detection. First, we demonstrate the existence of adaptation which is specific not merely to the direction of movement of an edge, but also to its contrast polarity. Second, it is shown that adaptation to a spatially homogeneous field whose luminance is modulated according to a temporal sawtooth waveform produces predictable changes in sensitivity to the movement of an edge; these changes, too, are specific to particular conjunctions of direction and edge polarity. Third, similar changes in sensitivity are demonstrated to occur when the luminance of an edge is physically perturbed at the moment of its displacement. Finally, it is shown that, as predicted, the sudden onset of an edge can itself give rise to a momentary impression of movement, the apparent direction of which depends upon the change in luminance that accompanies the onset of the edge.

Adaptation, Physiological↗
PubMed2006

Exposure to violence and mental health among Chinese American urban adolescents.

PURPOSE: This cross-sectional study examined exposure to violence as a predictor of mental health and perpetration of violence in a sample of 71 Chinese American young adolescents from nine urban middle schools. METHODS: Separate hierarchical multiple regressions were used to predict self-reported symptoms of depression and post-traumatic stress disorder (PTSD), perpetration of violence, and teacher-reported symptoms of anxiety, depression, and adaptive functioning. RESULTS: After controlling for daily hassles, exposure to violence uniquely predicted higher self-reported PTSD and depressive symptoms. After controlling for prior academic achievement and daily hassles, exposure to violence uniquely predicted more perpetration of violence. CONCLUSIONS: Our study suggests that exposure to violence is associated with worse mental health and more perpetration of violence among Chinese American adolescents living in urban areas.

Adolescent↗
PubMed2002

Cognitive style predictors of affect change in older adults.

Cognitive styles are the lenses through which individuals habitually process information from their environment. In this study, we evaluated whether different cognitive style individual difference variables, such as explanatory style and dispositional optimism, could predict changes in affective state over time in community-dwelling older adults. Based on previous research, we hypothesized that an optimistic explanatory style would be adaptive except when combined with life stressors, but that dispositional optimism would predict positive affective states regardless of life events. We found that older adults with a more optimistic explanatory style for health/cognitive events actually appeared to develop more depressive symptoms over six months of follow-up. However, dispositional optimism and orientation toward the future predicted a better affective profile over time.

Affect↗