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PubMed2005

Predictors of psychosocial adaptation among people with spinal cord injury or disorder.

OBJECTIVE: To examine the influence of disability-related medical and psychologic variables on psychosocial adaptation to spinal cord injury or disorder (SCI/D). DESIGN: A structural equation modeling design linking 3 sets of predictive variables to an outcome measure of adaptation. SETTING: Two outpatient SCI clinics (1 veteran, 1 civilian) in Texas. PARTICIPANTS: Veterans (n=181) and civilians (n=132) with SCI/D. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The adaptation outcome was measured by 2 subscales (acknowledgment, adjustment) of the Reactions to Impairment and Disability Inventory (RIDI) and by the Quality of Life Scale. The predictive variables were measured by a demographic questionnaire, 3 subscales (intrusion, re-experiencing, hyperarousal) of the Purdue Posttraumatic Stress Disorder-Revised scale, the McMordie-Templer Death Anxiety Scale, and 3 subscales (anxiety, depression, denial) of the RIDI. RESULTS: Goodness-of-fit indices suggested that a revised model of adaptation was a moderately good fit to the data. The revised model of adaptation indicated that there were medium total effects (direct plus indirect) on psychosocial adaptation by 2 latent variables (disability severity and impact, negative affectivity) and small total effects on psychosocial adaptation by disengagement coping. The latent factor of disengagement coping had the strongest direct effect on adaptation (although not statistically significant). Disability severity and impact had medium indirect effects and negative affectivity had small indirect effects on psychosocial adaptation. All of the aforementioned effects had a negative coefficient. CONCLUSIONS: Negative emotional responses (eg, depression, anxiety) to SCI/D, disengagement-type coping (eg, disability denial, avoidance), and the severity and impact of disability were related to lower levels of adaptation to SCI/D.

Adaptation, Psychological↗
PubMed2000

Cloning of the cDNA and localization of the gene encoding human NRBP, a ubiquitously expressed, multidomain putative adapter protein.

Adapter proteins modulate multiple signaling pathways by regulating the aggregation of other factors into signaling complexes. Here we have identified a novel human cDNA encoding NRBP, a multidomain putative adapter protein containing (i) two putative nuclear receptor binding motifs (LXXLL), (ii) a putative binding domain for Src homology-2 (SH2) domain containing proteins, (iii) a kinase-like domain, (iv) a bipartite nuclear localization signal, and (v) three sequences rich in glutamic acid, serine, proline, and threonine (PEST) residues. The NRBP mRNA transcript, of approximately 2.4 kb, was ubiquitously expressed in a wide range of normal human tissues and 15 human tumor cell lines. The NRBP cDNA is predicted to encode a polypeptide of 535 amino acids with a molecular mass of 59.8 kDa. Translation of NRBP mRNA in vitro reveals three translation products of 60, 51, and 43 kDa, suggesting that translation of NRBP may initiate at multiple sites. The NRBP gene was localized to human chromosome 2p23, near the location of the NCOA1 gene encoding the nuclear receptor coactivator, steroid receptor coactivator-1 (SRC-1). The features of NRBP predict a function as an adapter protein potentially linking signaling pathways involving nuclear receptors and SH2 domain containing proteins.

3' Untranslated Regions↗
PubMed2001

Confronting the winds: orientation and flight behaviour of roosting swifts, Apus apus.

Swifts, Apus apus, spend the night aloft and this offers an opportunity to test the degree of adaptability of bird orientation and flight to different ecological situations. We predicted the swifts' behaviour by assuming that they are adapted to minimize energy expenditure during the nocturnal flight and during a compensatory homing flight if they become displaced by wind. We tested the predictions by recording the swifts' altitudes, speeds and directions under different wind conditions with tracking radar; we found an agreement between predictions and observations for orientation behaviour, but not for altitude and speed regulation. The swifts orientated consistently into the head wind, with angular concentration increasing with increasing wind speed. However, contrary to our predictions, they did not select altitudes with slow or moderate winds, nor did they increase their airspeed distinctly when flying into strong head winds. A possible explanation is that their head-wind orientation is sufficient to keep nocturnal displacement from their home area within tolerable limits, leaving flight altitude to be determined by other factors (correlated with temperature), and airspeed to show only a marginal increase in strong winds. The swifts were often moving "backwards", heading straight into the wind but being overpowered by wind speeds exceeding their airspeed. The regular occurrence of such flights is probably uniquely associated with the swifts' remarkable habit of roosting on the wing.

Altitude↗
PubMed2004

Hybridization and adaptive radiation.

Whether interspecific hybridization is important as a mechanism that generates biological diversity is a matter of controversy. Whereas some authors focus on the potential of hybridization as a source of genetic variation, functional novelty and new species, others argue against any important role, because reduced fitness would typically render hybrids an evolutionary dead end. By drawing on recent developments in the genetics and ecology of hybridization and on principles of ecological speciation theory, I develop a concept that reconciles these views and adds a new twist to this debate. Because hybridization is common when populations invade new environments and potentially elevates rates of response to selection, it predisposes colonizing populations to rapid adaptive diversification under disruptive or divergent selection. I discuss predictions and suggest tests of this hybrid swarm theory of adaptive radiation and review published molecular phylogenies of adaptive radiations in light of the theory.

Journal Article↗
PubMed1998

Maladaptive achievement patterns: a test of a diathesis-stress analysis of helplessness.

The present study tested the assumptions, derived from a diathesis-stress model, that students' perceptions of autonomy-support in their classroom produce a relatively intrinsic as opposed to extrinsic motivational approach to academic tasks and that this approach, in turn, predicts qualitatively different responses to uncontrollable events. It was further assumed that students' motivational orientation would be more reliable than attributional style or perceptions of competence in predicting achievement patterns, including performance level after failure, use of adaptive attributions, and overall achievement scores. Results supported these predictions and further demonstrated, in longitudinal analyses, that motivational orientation may contribute to the formation of perceptions of competence and attributional style in students.

Achievement↗
PubMed2003

Extending backcalculation to analyse BSE data.

We review the origins of backcalculation (or back projection) methods developed for the analysis of AIDS (acquired immunodeficiency syndrome) incidence data. These techniques have been used extensively for >15 years to deconvolute clinical case incidence, given knowledge of the incubation period distribution, to obtain estimates of past HIV (human immunodeficiency virus) infection incidence and short-term predictions of future AIDS incidence. Adaptations required for the analysis of bovine spongiform encephalopathy (BSE) incidence included: stratification of BSE incidence by age as well as birth cohort; allowance for incomplete survival between infection and the onset of clinical signs of disease; and decomposition of the age- and time-related infection incidence into a time-dependent feed risk component and an age-dependent exposure/susceptibility function. The most recent methodological developments focus on the incorporation of data from clinically unaffected cattle screened using recently developed tests for preclinical BSE infection. Backcalculation-based predictions of future BSE incidence obtained since 1996 are examined. Finally, future directions of epidemiological analysis of BSE epidemics are discussed taking into account ongoing developments in the science of BSE and possible changes in BSE-related policies.

Animals↗
PubMed2005

Efferent-mediated adaptation of the DPOAE as a predictor of aminoglycoside toxicity.

Rapid efferent adaptation of the distortion product otoacoustic emission (DPOAE) predicts susceptibility to noise-induced damage, and is linked to the concentration of the efferent receptor (alpha9). Maximum adaptation occurs at intense primary levels, rapidly switching from positive to negative orientation in a very narrow (2 dB) range of F1 and F2 levels. Aminoglycosides are commonly used antibiotics, with the undesirable side-effect of ototoxicity. Susceptibility to hair cell damage from the aminoglycoside gentamicin can be quite variable, even within a single strain and species of animal. Since one of gentamicin's first sites of action in the outer hair cell (OHC) is at the efferent receptor, it is possible that efferent activity could be a predictor of susceptibility to gentamicin induced damage. Significant sex-related differences were found in two strains of guinea pigs when treated with gentamicin. Female guinea pigs were more susceptible both to systemic effects and to specific ototoxic effects. Efferent-mediated DPOAE adaptation served as a predictor of sensitivity to aminoglycoside damage, predicting both number of days before onset of deafness in male animals, and predicting final threshold shifts from gentamicin doses which produced variable results.

Adaptation, Physiological↗
PubMed2000

Predictive power of peer behavioral assessment for subsequent maladjustment in community samples of disruptive and nondisruptive children.

In a prospective, longitudinal study with community samples of disruptive and nondisruptive children, the predictive relations between peer-assessed dimensions of behavioral reputation in elementary school and teacher-rated behavioral adjustment and test scores of academic achievement were examined over a 4-year period. The Revised Class Play (RCP), a social role matching instrument completed by students about their classmates, was used to assess behavioral dimensions of children's peer reputation at baseline. Regression analyses showed that the RCP dimensions of aggressive-disruptive, sensitive-isolated, and social etiquette were the best predictors of later teacher-rated externalizing problems, internalizing problems, and subsequent adaptive skills respectively. Only IQ predicted later academic achievement. When IQ and disruptive/nondisruptive group status were added to each regression equation they further contributed as significant predictors. When parent and teacher ratings of behavior problems at baseline were entered jointly with RCP dimensions into regression equations, the peer dimensions further explained outcome variance. Additive effects of the RCP dimensions were found only for the externalizing problems outcome. Disruptive children with mild levels of aggressive behavior and high levels of sensitive-isolated behavior had less externalizing problems at outcome. A comparison of the difference between disruptive and nondisruptive groups in the relationship of baseline RCP scores to teacher outcomes showed no difference between groups, suggesting that the groups did not depart appreciably from their initial differences relative to each other over time.

Achievement↗
PubMed2025

Orthrus: Towards Evolutionary and Functional RNA Foundation Models.

In the face of rapidly accumulating genomic data, our ability to accurately predict key mature RNA properties that underlie transcript function and regulation remains limited. Pre-trained genomic foundation models offer an avenue to adapt learned RNA representations to biological prediction tasks. However, existing genomic foundation models are trained using strategies borrowed from textual domains that do not leverage biological domain knowledge. Here, we introduce Orthrus, a Mamba-based mature RNA foundation model pre-trained using a novel self-supervised contrastive learning objective with biological augmentations. Orthrus is trained by maximizing embedding similarity between curated pairs of RNA transcripts, where pairs are formed from splice isoforms of 10 model organisms and transcripts from orthologous genes in 400+ mammalian species from the Zoonomia Project. This training objective results in a latent representation that clusters RNA sequences with functional and evolutionary similarities. We find that the generalized mature RNA isoform representations learned by Orthrus significantly outperform genomic foundation models on mRNA property prediction tasks, and requires only a fraction of fine-tuning data to do so. Finally, we show that Orthrus is capable of capturing divergent biological function of individual transcript isoforms.

Journal Article↗
PubMed2006

Parasite local adaptation in a geographic mosaic.

A central prediction of the geographic mosaic theory of coevolution is that coevolving interspecific interactions will show varying degrees of local maladaptation. According to the theory, much of this local maladaptation is driven by selection mosaics and spatially intermingled coevolutionary hot and cold spots, rather than a simple balance between gene flow and selection. Here I develop a genetic model of host-parasite coevolution that is sufficiently general to incorporate selection mosaics, coevolutionary hot and cold spots, and a diverse array of genetic systems of infection/resistance. Results from this model show that the selection mosaics experienced by the interacting species are an important determinant of the sign and magnitude of local maladaptation. In some cases, this effect may be stronger than a previously described effect of relative rates of parasite and host gene flow. These results provide the first theoretical evidence that selection mosaics and coevolutionary hot and cold spots per se determine the magnitude and sign of local maladaptation. At the same time, however, these results demonstrate that coevolution in a geographic mosaic can lead to virtually any pattern of local adaptation or local maladaptation. Consequently, empirical studies that describe only patterns of local adaptation or maladaptation do not provide evidence either for or against the theory.

Adaptation, Physiological↗
PubMedDate not supplied

Predicting danger: the nature, consequences, and neural mechanisms of predictive fear learning.

The ability to detect and learn about the predictive relations existing between events in the world is essential for adaptive behavior. It allows us to use past events to predict the future and to adjust our behavior accordingly. Pavlovian fear conditioning allows anticipation of sources of danger in the environment. It guides attention away from poorer predictors toward better predictors of danger and elicits defensive behavior appropriate to these threats. This article reviews the differences between learning about predictive relations and learning about contiguous relations in Pavlovian fear conditioning. It then describes behavioral approaches to the study of these differences and to the examination of subtle variations in the nature and consequences of predictive learning. Finally, it reviews recent data from rodent and human studies that have begun to identify the neural mechanisms for direct and indirect predictive fear learning.

Adaptation, Psychological↗
PubMed2003

Rapid i.v. loading with phenytoin with subsequent dose adaptation using non-steady-state serum levels and a Bayesian forecasting computer program to predict maintenance doses.

OBJECTIVE: To evaluate the suitability of a phenytoin loading dose regimen; to assess whether dose-individualization was necessary and to investigate the reliability of a Bayesian forecasting method for phenytoin dose adaptation using non-steady-state levels in hospital-admitted patients. METHOD: An initial loading dose (15 mg phenytoin acid/kg BW) was given i.v. over 4 h, followed by standardized maintenance doses given i.v. in 12-h intervals from days 1 to 5 (175 mg </= 70 kg; 202 mg > 70 kg BW). The evening dose of day 5 was individualized based on three serum trough levels: L1 (after 16 h), L2 (morning day 4) and L3 (morning day 5). RESULTS: Ninety of 136 consecutive patients were evaluable in a prospective study for the standardized phase; 50 of them had additional serum levels in the individualized phase. There was no exclusion of patients with interacting co-medication. Seventy-seven per cent (L1) and 68% (L3) of patients showed therapeutic values (10-20 mg/L). The prediction error of the forecasting was 3.95 mg/L, the root mean squared error 6.27 mg/L (target trough level 11 mg/L). Seventy per cent of the levels (n=50) were within the 68% confidence interval. CONCLUSION: The effectiveness and safety of the regimen with rapid i.v. loading and the necessity to individualize phenytoin dosing after day 5 were demonstrated.

Adolescent↗
PubMedDate not supplied

ESB Research Award 1992. The mechanism of bone remodeling and resorption around press-fitted THA stems.

A major problem threatening the long-term integrity of total hip replacement is the loss of proximal bone often found around noncemented stems in the long term. It is generally accepted that 'stress shielding' is the cause for this problem: after implantation of the prosthesis the surrounding bone is partially 'shielding' from load carrying and starts to resorb. One of the proposed answers to this problem is the application of press-fitted stems. These smooth-surfaced implants are thought to provoke higher proximal bone loading, and, hence, less stress shielding than bonded implants, because they are wedged into the femur every time when loaded. However, in a two-year experiment in dogs, similar amounts of resorption of the proximal cortex were found around press-fitted and bonded implants. The question arises how similar resorption patterns can develop under completely different stress conditions, and whether this phenomenon can be explained by adaptive bone remodeling theories based on Wolff's law. In the present study an answer was sought for this question. An advanced iterative computer simulation model was used to analyze the remodeling process in the animal experiment. Three-dimensional finite element models were constructed from the animal experimental configuration, in which smooth, press-fitted stems were applied unilaterally in the canine. The FE model was integrated with iterative remodeling procedures, validated in earlier studies. In the model an appropriate non-linear representation of the loose bone-implant interface was realized, also capable of simulating the proximal interface gap that was found around the uncoated implants. The simulation models predicted similar amounts of proximal bone loss and distal bone densification as found in the animal model. Hence, the cortical bone loss could indeed be predicted by the strain-adaptive bone remodeling theory. By unraveling the simulation process, the question stated above could be answered. Densification of the distal bone bed during the initial remodeling process was found to cause reduced axial stem displacement (elastic subsidence), decreasing the wedging effect of the stem and, hence, decreasing the loading of the proximal bone, resulting in proximal bone loss. Hence, whereas in the case of bonded stems the proximal resorption process develops monotonously to a new equilibrium, the process around smooth, press-fitted stems develops nonmonotonously. This is due primarily to the unbonded interface conditions and the development of a proximal fibrous membrane. The remodeling process then gradually causes the stem to be jammed in the distal diaphyses (proximal 'stress bypass').

Alloys↗
PubMed2006

How to be early flowering: an evolutionary perspective.

In wild and cultivated annual plant species, flowering time is an important life-history trait that coordinates the life cycle with local environmental conditions. Extensive studies on the genetic basis of flowering time in the model species Arabidopsis thaliana have revealed a complex genetic network that can detect environmental and internal signals. Based on this knowledge and on known pleiotropic effects associated with flowering time genes, we suggest that a natural shift towards an early-flowering life cycle might involve only particular functional regions in a limited number of genes. Our predictions are supported by genetic theories of adaptation and by recent data about genes associated with natural variation. We analyse the extent to which these predictions can also apply to crop species.

Adaptation, Biological↗
PubMed1995

An automated computer vision and robotics-based technique for 3-D flexible biomolecular docking and matching.

The generation of binding modes between two molecules, also known as molecular docking, is a key problem in rational drug design and biomolecular recognition. Docking a ligand, e.g., a drug molecule or a protein molecule, to a protein receptor, involves recognition of molecular surfaces as molecules interact at their surface. Recent studies report that the activity of many molecules induces conformational transitions by 'hinge-bending', which involves movements of relatively rigid parts with respect to each other. In ligand-receptor binding, relative rotational movements of molecular substructures about their common hinges have been observed. For automatically predicting flexible molecular interactions, we adapt a new technique developed in Computer Vision and Robotics for the efficient recognition of partially occluded articulated objects. These type of objects consist of rigid parts which are connected by rotary joints (hinges). Our approach is based on an extension and generalization of the Geometric Hashing and Generalized Hough Transform paradigm for rigid object recognition. Unlike other techniques which match each part individually, our approach exploits forcefully and efficiently enough the fact that the different rigid parts do belong to the same flexible molecule. We show experimental results obtained by an implementation of the algorithm for rigid and flexible docking. While the 'correct', crystal-bound complex is obtained with a small RMSD, additional, predictive 'high scoring' binding modes are generated as well. The diverse applications and implications of this general, powerful tool are discussed.

Algorithms↗
PubMed1990

Stress adaptation and low-frequency impedance of rat lungs.

At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed2006

Local and global costs of adaptive plasticity to density in Arabidopsis thaliana.

Although phenotypic plasticity is demonstrably adaptive in a range of settings, organisms are not perfectly plastic. Costs of plasticity comprise one factor predicted to counter the evolution of this adaptive strategy, yet evidence of costs is rare. Here, we test the fitness effects of plastic life-history and morphological responses to density and costs of this plasticity in recombinant inbred lines of Arabidopsis thaliana. Several costs of plasticity and homeostasis were detected. Of particular relevance, there was a significant cost of plasticity to active stem-elongation responses, an adaptive trait in many species. There was also a cost of plasticity to apical branch production at both high and low density, which resulted from the greater suppression of basal branching in genotypes with plastic apical branch production relative to genotypes with fixed apical branch production. The presence of a cost in multiple environments (i.e., a global cost) is predicted to counter the evolution of plasticity. Experimental segregating progenies such as the one used here are expected to have higher genetic costs of plasticity than arrays of genotypes sampled from natural populations because selection should remove genotypes with costs resulting from linkage disequilibrium or epistasis. The use of experimental progeny arrays therefore increases the ability to evaluate genetic costs.

Adaptation, Physiological↗
PubMed1999

Sociality and social learning in two species of corvids: the pinyon jay (Gymnorhinus cyanocephalus) and the Clark's nutcracker (Nucifraga columbiana).

The hypothesis that social learning is an adaptive specialization for social living predicts that social species should learn better socially than they do individually, but that nonsocial species should not exhibit a similar enhancement of performance under social learning conditions. The authors compared individual and social learning abilities in 2 corvid species: the highly social pinyon jay (Gymnorhinus cyanocephalus) and the less social Clark's nutcracker (Nucifraga columbiana). The birds were tested on 2 different tasks under individual and social learning conditions. Half learned a motor task individually and a discrimination task socially; the other half learned the motor task socially and the discrimination task individually. Pinyon jays learned faster socially than they did individually, but nutcrackers performed equally well under both learning conditions. Results support the hypothesis that social learning is an adaptive specialization for social living in pinyon jays.

Analysis of Variance↗