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PubMed2006

Unique folding of precursor microRNAs: quantitative evidence and implications for de novo identification.

MicroRNAs (miRNAs) participate in diverse cellular and physiological processes through the post-transcriptional gene regulatory pathway. Hairpin is a crucial structural feature for the computational identification of precursor miRNAs (pre-miRs), as its formation is critically associated with the early stages of the mature miRNA biogenesis. Our incomplete knowledge about the number of miRNAs present in the genomes of vertebrates, worms, plants, and even viruses necessitates thorough understanding of their sequence motifs, hairpin structural characteristics, and topological descriptors. In this in-depth study, we investigate a comprehensive and heterogeneous collection of 2241 published (nonredundant) pre-miRs across 41 species (miRBase 8.2), 8494 pseudohairpins extracted from the human RefSeq genes, 12,387 (nonredundant) ncRNAs spanning 457 types (Rfam 7.0), 31 full-length mRNAs randomly selected from GenBank, and four sets of synthetically generated genomic background corresponding to each of the native RNA sequence. Our large-scale characterization analysis reveals that pre-miRs are significantly different from other types of ncRNAs, pseudohairpins, mRNAs, and genomic background according to the nonparametric Kruskal-Wallis ANOVA (p<0.001). We examine the intrinsic and global features at the sequence, structural, and topological levels including %G+C content, normalized base-pairing propensity P(S), normalized minimum free energy of folding MFE(s), normalized Shannon entropy Q(s), normalized base-pair distance D(s), and degree of compactness F(S), as well as their corresponding Z scores of P(S), MFE(s), Q(s), D(s), and F(S). The findings will promote more accurate guidelines and distinctive criteria for the prediction of novel pre-miRs with improved performance.

Animals↗

PubMed1997

Improved ultrastructural preservation of bioprosthetic tissue.

BACKGROUND AND AIMS OF THE STUDY: Poor ultrastructural tissue preservation of bioprosthetic heart valves is associated with a higher propensity for calcification. In spite of this realization, commercial valve fixation remains suboptimal. METHODS: In an attempt to maintain tissue integrity through improved cross-linking procedures, transmission electron microscopy and a 21-point damage score were applied to assess the ultrastructural preservation of aortic wall tissue-the main component of contemporary aortic valve bioprostheses. An ideal glutaraldehyde (GA) concentration was assessed by immediate tissue fixation at 4 degrees C comparing 0.2%, 0.5%, 0.65%, 1.0%, 2.0%, 3.0% and 4.0% GA in phosphate-buffered saline (PBS). Subsequently, an optimal concentration of 3.0% GA was used to determine the effect of fixation temperature (4 degrees, 22 degrees and 37 degrees C). Finally, the superior glutaraldehyde concentration (3.0%) and cross-linking temperature (4 degrees C) were used to assess tolerance towards delayed fixation. RESULTS: When different GA concentrations were used almost identical damage scores of 6.3 and 5.8 were found for 0.2% and 0.65% fixation. The first significant improvement was found at a concentration of 1.0% (score 3.3; p < 0.01) followed by a further improvement at 3.0% (score 2.6; p = 0.05). The optimal fixation temperature was 4 degrees C (3.7) with the worst results obtained at room temperature (score 9.2; p < 0.03). When fixation was delayed, the most significant damage occurred during the initial 30 min after slaughter (from 2.3 to 7.4; p < 0.02) followed by another significant deterioration between 4 and 16 h (from 5.6 to 9.7; p < 0.02). CONCLUSIONS: In summary, the prerequisites for an ideal ultrastructural preservation of bioprosthetic aortic wall tissue are immediate fixation (within 30 min), high GA concentrations (> 1.0%) and cold-temperature fixation (4 degrees C).

Animals↗

PubMed2002

Sleep propensity varies with behaviour and the situation in which it is measured: the concept of somnificity.

It is self-evident that we fall asleep more readily when lying down than when standing up. Nevertheless, the influence of this and more subtle changes in posture, activity and the situation in which sleep propensity is measured have been largely ignored. The term somnificity is introduced here, defined as the general characteristic of a posture, activity and situation that reflects its capacity to facilitate sleep-onset in a majority of subjects. The relative somnificities of different activities and situations in the Epworth Sleepiness Scale (ESS) were investigated in 23 groups, involving 2802 subjects from seven different countries. The means of the different ESS item-scores were ranked from highest to lowest in each group. There was a high concordance (Kendall's C=0.84, P < 0.0001) among these ranks for all groups, whether of normal subjects or patients with sleep disorders, regardless of age, sex, or average sleepiness in daily life assessed by total Epworth scores. The ESS item-ranks formed an ordinal scale of somnificities with five different levels. Analysis of raw ESS item-scores for all 987 individual Australian subjects showed the same pattern of somnificities with six different levels, but with a lower concordance (C=0.39, P < 0.0001). This was probably because of subject x situation-specific interactions that were averaged within groups. A conceptual model of sleepiness is outlined that includes interactions between separate sleep and wake drives as a possible way of including behavioural and situational influences on sleep propensity.

Adolescent↗

PubMed2003

Gender, kinship and caregiver burden: the case of community-dwelling memory impaired seniors.

BACKGROUND: This study examined whether there were gender and kinship (spouse, child, more distant relative) differences in caregiver burden. It further examined the constellation of gender and kinship by examining whether adult daughter caregivers experienced greater burden compared to wives, husbands, sons, and other more distant relatives. METHODS: The sample consisted of 305 family caregivers of memory-impaired individuals who were age 70 years or older and resided in non-institutional settings in Arkansas. A cross-sectional design was employed using validated measures to assess both the memory-impaired elders' and family caregivers' self-reported physical and memory status. RESULTS: After controlling for the age and health status characteristics of the memory-impaired elder, sociodemographic and health status characteristics of the family caregiver, and the caregiver coping response (measured by the sense of coherence), multiple regression analyses found kinship, but not gender differences in caregiver burden. Adult children experienced more caregiver burden than more distant relatives. There were no significant differences in caregiver burden between adult children and spouses. Adult daughters had greater caregiver burden scores compared to more distant relatives, but had comparable scores to wives, sons, and husbands. Other significant correlates of burden included caregiver personal characteristics (age and ethnicity) and the sense of coherence. CONCLUSIONS: The study discusses the practice implications of adult children and adult daughters' propensity to suffer burden when caring for their memory-impaired parents living in the community. It also discusses the relevance of caregiver personal characteristics and the sense of coherence as correlates of burden.

Adolescent↗

PubMed2005

Aggressive/hostile personality traits and injury accidents: an eight-year prospective study of a large cohort of French employees -- the GAZEL cohort.

BACKGROUND: Aggressiveness on the roads and/or anger behind the wheel are considered to be a major traffic safety problem in several countries. However, the psychological mechanisms of anger and/or aggression on the roads remain largely unclear. This study examines a large cohort of French employees followed over the period 1994-2001 to establish whether psychometric measures of aggression/hostility were significantly associated with an increased risk of an injury accident (I-A). An I-A was defined as a traffic accident in which someone was injured, that is required medical care. METHOD: A total of 11,754 participants aged from 39 to 54 years in 1993 were included in this study. Aggression/hostility was measured in 1993 using the French version of the Buss-Durkee Hostility Inventory (BDHI). Driving behaviors and I-A were recorded in 2001. Sociodemographic and alcohol consumption data were available from annual follow-up of the cohort. The relationship between aggression/hostility scores and I-A was assessed using negative binomial regression models with time-dependent covariates. RESULTS: The overall BDHI scoring was not statistically predictive of subsequent I-A: adjusted rate ratio (aRR) 1.02, 95% confidence interval (CI) 0.81-1.28, for participants with intermediate scores and aRR 1.25, 95% CI 0.98-1.61 for those with high scores, both compared to those with low scores. The only BDHI subscales found to be associated with I-A were 'irritability' (aRR 1.33, 95% CI 1.02-1.75 for participants with high scores) and 'negativism' (aRR 1.32, 95% CI 1.01-1.71 for participants with high scores). CONCLUSION: Overall aggression/hostility personality traits did not predict I-A in this large cohort of French employees, suggesting that aggressiveness on the roads and/or anger behind the wheel extend beyond the individual's general propensity for aggression.

Accidents, Traffic↗

PubMed1998

Identifying dissociative identity disorder: a self-report and projective study.

This study compared 21 female adult psychiatric patients diagnosed with dissociative identity disorder (DID) with 21 female adult nondissociative psychiatric patients to determine whether DID patients exhibit a distinguishing set of clinical features, and perceptual, attentional, and cognitive processes. Participants were assessed with the Dissociative Disorders Interview Schedule to assess diagnostic status. Group scores on the Dissociative Experiences Scale, Tellegen Absorption Scale, Childhood Trauma Questionnaire, Brief Symptom Inventory, and the Rorschach test were compared. DID participants reported earlier and more severe childhood trauma, more dissociative symptoms, and a greater propensity for altered states of consciousness. The DID participants also exhibited increased projective and imaginative activity, a diminished ability to integrate mental contents, a complex and driven cognitive style, and a highly unconventional view of reality.

Adult↗

PubMed1994

Myelodysplasia.

Myelodysplasia or myelodysplastic syndromes represent a heterogeneous group of bone marrow disorders characterized by dysmaturation, cytopenias, and a propensity for leukemic transformation. Although universally adopted, the French-American-British classification still has several limitations and an inability to categorize all patients. Refinements in morphologic and histologic interpretation in addition to the use of scoring systems may improve diagnostic and prognostic capability. Cytogenetics and molecular genetic abnormalities are providing clues to the fundamental pathogenesis of myelodysplastic syndromes. However, the lesions responsible for initiation or disease progression are as yet unresolved. Although chemotherapy and allogeneic transplantation may be used in selected patients, the mainstay of therapy remains supportive care, with differentiating therapy being largely disappointing so far and the role of hematopoietic growth factors remaining unresolved.

Chromosome Aberrations↗

PubMed1996

Modelling inequality in reported long term illness in the UK: combining individual and area characteristics.

STUDY OBJECTIVE: To assess the nature of the relation between health and social factors at both the aggregated scale of geographical areas and the individual scale. DESIGN AND SETTING: The individual data are derived from the sample of anonymised records (SAR) from the census of 1991 in Great Britain, and are combined with area data from this census. The ecological setting (context) was defined using multivariate methods to classify the 278 districts of residence identifiable in the SAR. The outcome health variable is the 1991 census long-term limiting illness question. Health variations were analysed by multilevel logistic regression to examine the compositional variation (at the level of the individual) and the contextual variation (variability operating at the level of districts) in reported illness. PARTICIPANTS: 10 per cent randomised subsample of the SAR who are aged 16+ and are resident in households. MAIN RESULTS: The multi-level modelling revealed that area factors have a significant association with individual health outcome but their effect is smaller than that of individual attributes. The results show evidence for both compositional and contextual effects in the pattern of variation in propensity to report illness. CONCLUSIONS: The results suggest generally higher levels of ill health for individuals who are older, not married, in a semi/unskilled manual social class, and socioeconomically deprived (as measured by a composite deprivation score). All individuals living in areas with high levels of illness (which tend to be more deprived areas) show greater morbidity, even after allowing for their individual characteristics. However, within affluent areas, where morbidity was generally lower, the health inequality (health gradient) between rich and poor individuals was particularly strong. We consider the implications of these findings for health and resource allocation policy.

Adolescent↗

PubMed2002

Effect of spirituality on successful recovery from spinal surgery.

BACKGROUND: Many patients believe prayer helps them recover from health problems. Benefits of spirituality on other illnesses and surgical procedures have been reported. It is unknown whether patients with strong spiritual beliefs have a greater propensity for successful recovery from spinal surgery. METHODS: In this study, 188 patients having spinal surgery completed the visual analog pain scale (VAS) and the Oswestry functional capacity questionnaire (OSW) before and after operation, and the scores were used to assess surgical outcome. Degree of spirituality was assessed using the INSPIRIT survey. RESULTS: Paired t test revealed significant improvements in both the VAS and OSW outcome measures. Linear regression analysis revealed no correlation between change in either VAS or OSW. CONCLUSIONS: These results suggest that recovery from spinal surgery may be more dependent on proper patient selection and surgical technique than on patient spiritual beliefs.

Humans↗

PubMed2003

The onset and time course of response of negative symptoms to add-on fluvoxamine treatment.

Not enough is known about the propensity of individual negative symptoms to respond to treatment and the dynamics of this change. We have previously shown that adding the selective serotonin reuptake inhibitor fluvoxamine to antipsychotics can improve negative symptoms, and now provide data on the response of individual negative symptoms to such treatment. We examined items on the Schedule for the Assessment of Negative Symptoms for patients participating in two published controlled studies comparing the effect of add-on fluvoxamine and placebo on negative symptoms. Using a mixed regression model, we analysed item scores at each week of the study to identify the first signs of a treatment effect. Potential confounding effects of depressive extrapyramidal and positive symptoms were statistically controlled. Eleven of 16 items tested showed improvement, five within 2 weeks and a further four within 3 weeks of starting treatment. The most rapidly responding items included core negative symptoms such as alogia. The propensity for and rate of improvement with fluvoxamine treatment differs for the various negative symptoms. Many symptoms, including those generally agreed to be core features of the illness such as alogia, improved within 2-3 weeks of treatment initiation.

Antipsychotic Agents↗

PubMed2001

Computer-assisted re-design of spectrin SH3 residue clusters.

We have developed a protein design computer program, called Perla, which performs searches in sequence space to uncover optimal amino acid sequences for desired protein three-dimensional structures. Optimal sequences are localised at the minima of a sequence-structure energy landscape defined using a complex scoring function (an all-atom molecular mechanics force field plus statistical terms including entropy and solvation) measured with respect to a reference state simulating a denatured protein. Sequence choices eventually optimise side chain packing, secondary structure propensities, and hydrogen bonding and electrostatics interactions. Perla was used to re-design clusters of residues of the SH3 domain of alpha-spectrin. Several mutant proteins were produced and characterised. Some of our designed proteins have significantly higher stabilities (stability enhancements about 0.25, 0.70 and 1.0 kcal mol(-1)) than the wild-type protein. These successful protein re-designs, and similar examples found in the literature, establish the quality of the structure-based computational approach to protein design.

Algorithms↗

PubMed2004

Influence of selected hormonal and lifestyle factors on familial propensity to ovarian cancer.

AIM: To study the influence of established risk factors for ovarian cancer in women with a family history of ovarian and/or breast cancer. METHODS: Italian hospital-based case-control study. Cases were 1031 women with incident epithelial ovarian cancer and controls were 2411 women. Two "Adult life risk scores" (ALRS) were defined combining the effect of hormonal and lifestyle risk factors. RESULTS: Ovarian cancer risk increased with low number of children, late menopause, never or short oral contraceptive use, physical inactivity, rich red meat intake and low fish, pulse and vegetable intake. For hormonal factors, compared to women without a family history and low ALRS, the odds ratios (OR) was 1.77 for women without family history and high ALRS, 2.51 for women with family history and low ALRS and 5.99 for women with family history and high ALRS. The corresponding values for the lifestyle ALRS were 2.00, 2.24 and 7.43. CONCLUSIONS: Intervention on selected hormonal and lifestyle risk factors might be more important for women with family history of ovarian and/or breast cancer.

Adolescent↗

PubMed2000

Male signalling and lek attractiveness in the Mediterranean fruit fly.

I tested the null hypothesis that females of the Mediterranean fruit fly, Ceratitis capitata, were equally likely to visit leks composed of males with high versus low mating success. In laboratory trials, the observed distribution of matings among males differed significantly from that expected by chance, owing primarily to the higher than expected numbers of individuals with low (mated 0-1 days over 6 consecutive observation days) or high (mated 4 or more days) mating scores. I termed these two groups as 'low' and 'high' maters, respectively. In the field, greater numbers of female sightings were made at artificial leks of high maters than low maters. This result apparently reflected a greater calling propensity among high maters. Slopes of female sightings versus calling level did not differ significantly between leks of low and high maters, suggesting that the observed relationship between calling activity and female sightings was independent of male mating status. Following the same protocol, I conducted a second experiment to examine whether males used the signals of conspecific males to locate lek sites and, if so, whether signal attractiveness varied with male mating ability. Attraction of males to calling conspecifics was far weaker than that observed for females, and over five different trials a total of only seven male sightings were made at any of the established leks. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed2000

Evidence of a disposition toward fearfulness and vulnerability to posttraumatic stress in dysfunctional pain patients.

Few investigations have addressed whether patient subgroups derived using the Multiaxial Assessment of Pain (MAP) [Turk, D. C., & Rudy, T. E. (1987). Towards a comprehensive assessment of chronic pain patients. Behaviour Research and Therapy, 25, 237-249; Turk, D. C., & Rudy, T. E. (1988). Toward an empirically derived taxonomy of chronic pain patients: integration of psychological assessment data. Journal of Consulting and Clinical Psychology, 56, 233-238.] differ with regard to fear and avoidance. It has, however, been reported that dysfunctional patients exhibit more pain-specific fear and avoidance than patients classified as interpersonally distressed or minimizers/adaptive copers [Asmundson, G. J. G., Norton, G. R., & Allerdings, M. D. (1997). Fear and avoidance in dysfunctional chronic back pain patients. Pain, 69, 231-236.]. We attempted to extend these findings by examining two fear constructs that are receiving increased attention in the chronic pain literature-anxiety sensitivity and PTSD. The sample comprised 115 patients with chronic pain. Of these, 14 (12.2%) were classified as dysfunctional, 21 (18.3%) as interpersonally distressed and 47 (40.8%) as minimizers/adaptive copers. Between-group differences were observed on the fear of cognitive and emotional dyscontrol dimension of anxiety sensitivity, total and symptom cluster scores on the PTSD measure, and depression. No differences were observed for the fear of somatic sensations dimension of anxiety sensitivity or agoraphobia, social phobia, and blood/injury fears. Dysfunctional patients generally exhibited elevated scores relative to one or both of the other MAP subgroups on fear of cognitive and emotional dyscontrol, depressed affect, PTSD symptom total score and PTSD symptom cluster scores. As well, a substantial proportion of dysfunctional and interpersonally distressed patients were classified as having PTSD (71.4 and 42.9%, respectively) when compared to minimizers/adaptive copers (21.3%). These results suggest that MAP subgroups differ with regard to their propensity to be(come) fearful and in their likelihood of having PTSD. Theoretical and clinical implications are discussed.

Adaptation, Psychological↗

PubMed1999

Evaluation of the fluorometric protein phosphatase inhibition assay in the determination of okadaic acid in mussels.

The protein phosphatase inhibition assay for okadaic acid, the major DSP toxin, modified to use the fluorescence substrates methylumbelliferyl phosphate (MUP) and fluorescein diphosphate (FDP), was compared to the assay using p-nitrophenylphosphate (p-NPP) and the bioluminescence assay using luciferin phosphate (L-P). Under the standard assay conditions used okadaic acid inhibited the enzyme activity dose-dependently with IC50 values of 1.5 nM (MUP) and 1.2 nM (FDP). This compares to IC50 values of 0.9 and 6 nM using L-P and p-NPP respectively. CDP-star, a chemiluminescence substrate, was not hydrolysed by the enzyme. Decreasing the enzyme concentration lowered the IC50 for the colorimetric method (IC50=2 nM [p-NPP], 0.75 nM enzyme) but no shift was observed with fluorimetry. However at enzyme concentrations < 1.5 nM (standard assay) the error margin was too great for routine analysis. The method using fluorimetry allowed detection of okadaic acid concentrations to levels < or = 1 microg/100 g of mussel tissue which is well below the limit of 20 microg/100 g (mouse bioassay) set by some regulatory agencies. Determination of the toxin content in naturally contaminated mussels in three separate experiments gave coefficients of variance ranging from 16 to 29% (MUP) and from 8 to78% (p-NPP). Multicomparison studies showed that concentrations of okadaic acid in naturally contaminated mussel samples determined by fluorescence generally agreed with those obtained using ELISA and LC-MS procedures, and with the mouse bioassay. However using the mouse bioassay as the standard, values determined by the ELISA, PP-2A and LC-MS all scored false negative results compared to those for the mouse bioassay in the range 20-40 microg/100 g mussel, and at the limit of the mouse bioassay the values by the other three methods were substantially less. With few exceptions the methods scored okadaic acid with highest to lowest values in the following order: mouse bioassay > ELISA > PP-2A > LC-MS. The fluorimetric assay was both more sensitive and accurate than the colorimetric assay (the latter showed a propensity towards false positives in the region 20 microg/100 g), and the moderate increase in equipment cost appears to be outweighed by the performance of the method.

Animals↗

PubMed1995

Propensity for seeking counseling services: a comparison of Asian and American undergraduates.

The authors used the somaticization scale of the Brief Symptom Inventory to study Asian and American college students' propensity for seeking counseling at an American university. They found that the Asian students were more likely than the American students were to report that they would seek counseling services when they experience somatic discomfort. The Asian students scored significantly higher on inclination for seeking counseling than did the American students.

Asia↗

PubMed1997

Prediction of the stability of protein mutants based on structural environment-dependent amino acid substitution and propensity tables.

An approach to the prediction of mutant stability is described using knowledge of amino acid replacements that are tolerated within the families of homologous proteins of known 3-D structure. Amino acid variations in families of homologous proteins are converted to propensity and substitution tables; these provide quantitative information about the existence of an amino acid in a structural environment and the probability of replacement by any other amino acid. The tables are used to calculate a 'stability difference score', analogous to the difference in free energy between a mutant and the wild type. The method has been developed and tested using the high-resolution structures for T4 lysozyme and 159 site-specific mutants. We show that differences in stability scores are correlated with experimentally observed free energy differences and differences in melting temperature. Blind tests, using only structural information derived from the parent wild-type crystal structures, on a combined set of 83 staphylococcal nuclease and 68 barnase mutants showed a correlation of 0.80 in the predicted stability changes with experimental thermodynamic data. Approximately 86% of the predictions were correctly classified as destabilizing or stabilizing.

Algorithms↗

PubMed1994

Sleepiness in different situations measured by the Epworth Sleepiness Scale.

This investigation examines how the sleep propensity (SP) in one test situation, such as the Multiple Sleep Latency Test (MSLT), is related to sleepiness in daily life, as assessed by the Epworth Sleepiness Scale (ESS). This is a self-administered questionnaire, the item scores from which provide a new method for measuring SPs in eight different real-life situations. The ESS item scores were analyzed separately in four groups of subjects: 150 adult patients with a variety of sleep disorders, 87 medical students who answered the ESS on two occasions 5 months apart, 44 patients who also had MSLTs and 50 patients whose spouses also answered the ESS about their partner's sleepiness. The ESS item scores were shown to be reliable (mean rho = 0.56, p < 0.001). The SP measured by the MSLT was related to three of the eight item scores in a multiple regression (r = 0.64, p < 0.001). The results of nonparametric ANOVA, Spearman correlations, Wilcoxon's t tests, item and factor analysis suggest that individual measurements of SP involve three components of variation in addition to short-term changes over periods of hours or days: a general characteristic of the subject (his average SP), a general characteristic of the situation in which SP is measured (its soporific nature) and a third component that is specific for both subject and situation. The SP in one test situation, including the MSLT, may not be a reliable indicator of a subject's average SP in daily life. Perhaps we should reexamine the current concept of daytime sleepiness and its measurement.

Adult↗