Gene expression profiling of cells, tissues, and developmental stages of the nematode C. elegans.
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Animals↗
Biomedical subjects
D L Riddle
Publications and source records attributed to D L Riddle.
LG II balancer chromosomes in Caenorhabditis elegans: mT1(II;III) and the mIn1 set of dominantly and recessively marked inversions.
Two new genetic balancers for chromosome II of Caenorhabditis elegans were isolated and characterized. mIn1 was shown to be an inversion of a large central portion of the chromosome, extending from lin-31 to rol-1, that includes most of the genes on the chromosome. It balances a region to the left of the gene cluster that was previously not covered by any of the available balancers. mIn1 recombines efficiently with the normal chromosome II in regions outside the rearrangement at both ends, and appears to enhance recombination frequency adjacent to the inversion breakpoints. Eight variant strains of mIn1 were isolated, including forms that carry recessive morphological or lethal markers, an unmarked form, and one that carries an integrated transgene that confers a semi-dominant green fluorescent protein (GFP) phenotype. This set of variants makes mIn1 useful for a wide variety of applications. The second balancer, mT1, was shown to be a II;III translocation that suppresses recombination on the right arms of chromosomes II and III. It balances chromosome II from the region between bli-2 and dpy-10 to the right end of the chromosome, and chromosome III from the region between daf-2 and unc-93 to the right end. These rearrangements provide the means to stabilize efficiently most of the genes on chromosome II, and may be useful for studies of chromosome pairing and recombination.
Animals↗
Use of SF-36 and SF-12 health status measures: a quantitative comparison for groups versus individual patients.
BACKGROUND: The extent to which SF-12 scores reflect SF-36 scores has not been well studied. OBJECTIVES: One purpose was to compare the sensitivity to change of the SF-36 Physical Function sub-score, and the Physical Component Summary Scores (PCS) of the SF-36 and SF-12 on patients with low back pain (LBP). A second purpose was to determine if the SF-12 could serve as a surrogate measure for the SF-36 when making decisions about individual patients. SUBJECTS: The sample consisted of 101 consecutive patients. MEASURES: SF-36 questionnaires were completed by patients at both initial and discharge examinations. SF-12 scores were calculated from the completed SF-36 questionnaires. Therapists' judgments of whether patients were judged to have returned to premorbid function served as the construct for meaningful clinical change. ANALYSIS: Receiver Operating Characteristic (ROC) curve analysis and repeated measures MANCOVA were used to assess sensitivity to change. Linear regression and 95% prediction bands described the extent to which SF-12 scores predict individual SF-36 scores. RESULTS: No significant differences were found between the ROC curve areas for the Physical Function sub-scale, the PCS-36 and PCS-12. No significant differences were found for the comparison of change scores between PF-36, PCS-36 and PCS-12 scores. CONCLUSION: The findings suggest that Physical Function sub-scores, SF-36 and SF-12 PCS scores are equally sensitive to change. SF-12 PCS scores do not adequately predict SF-36 PCS scores for individual patients. The PCS-12 should probably not be used to make judgments about the health status of individual patients with LBP.
Activities of Daily Living↗
Changes in gene expression associated with developmental arrest and longevity in Caenorhabditis elegans.
Gene expression in a developmentally arrested, long-lived dauer population of Caenorhabditis elegans was compared with a nondauer (mixed-stage) population by using serial analysis of gene expression (SAGE). Dauer (152,314) and nondauer (148,324) SAGE tags identified 11,130 of the predicted 19,100 C. elegans genes. Genes implicated previously in longevity were expressed abundantly in the dauer library, and new genes potentially important in dauer biology were discovered. Two thousand six hundred eighteen genes were detected only in the nondauer population, whereas 2016 genes were detected only in the dauer, showing that dauer larvae show a surprisingly complex gene expression profile. Evidence for differentially expressed gene transcript isoforms was obtained for 162 genes. H1 histones were differentially expressed, raising the possibility of alternative chromatin packaging. The most abundant tag from dauer larvae (20-fold more abundant than in the nondauer profile) corresponds to a new, unpredicted gene we have named tts-1 (transcribed telomere-like sequence), which may interact with telomeres or telomere-associated proteins. Abundant antisense mitochondrial transcripts (2% of all tags), suggest the existence of an antisense-mediated regulatory mechanism in C. elegans mitochondria. In addition to providing a robust tool for gene expression studies, the SAGE approach already has provided the advantage of new gene/transcript discovery in a metazoan.
Animals↗
Using published evidence to guide the examination of the sacroiliac joint region.
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Humans↗
Development and initial validation of the back pain functional scale.
STUDY DESIGN: A prospective repeated-measures design was applied. OBJECTIVES: To examine the measurement properties of the Back Pain Functional Scale (BPFS) and the Roland-Morris Questionnaire (RMQ) and to formulate hypotheses and sample size estimates for a subsequent comparison study. SUMMARY OF BACKGROUND DATA: Although there are numerous functional status measures for patients with low back pain, most have been conceived of and validated with a group rather than an individual patient as the unit of interest. Also, little has been done to formally compare-this includes the generation of a priori hypotheses, followed by statistical hypotheses testing-the many competing measures. METHODS: Subjects were 77 patients with low back pain who were referred by physicians to 10 outpatient physical therapy clinics located in Canada and the United States. The questionnaires were administered at patients' initial visits, within 48 hours of the initial visit, and at 1-, 2-, and 3-week follow-up visits. Reliability, cross-sectional validity, and longitudinal validity (sensitivity to change) coefficients were calculated. RESULTS: Test-retest reliability estimates of 0.81 and 0. 88 were obtained for the RMQ and BPFS, respectively. The measures demonstrated similar levels of cross-sectional validity. Correlations of 0.56 and 0.65 were noted between a prognostic rating of change and the RMQ and BPFS, respectively. The RMQ demonstrated a ceiling effect. Approximately 180 patients are needed for a subsequent head-to-head comparison study of the measures. CONCLUSIONS: The BPFS appears to have sound measurement properties, and a formal head-to-head comparison study with the RMQ is warranted.
Adolescent↗
daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans.
The daf-12 gene acts at the convergence of pathways regulating larval diapause, developmental age, and adult longevity in Caenorhabditis elegans. It encodes a nuclear receptor most closely related to two C. elegans receptors, NHR-8 and NHR-48, Drosophila DHR96, and vertebrate vitamin D and pregnane-X receptors. daf-12 has three predicted protein isoforms, two of which contain DNA- and ligand-binding domains, and one of which contains the ligand-binding domain only. Mutations cluster in DNA- and ligand-binding domains, but correspond to distinct phenotypic classes. DAF-12 is expressed widely in target tissues from embryo to adult, but is upregulated during midlarval stages. In the adult, expression persists in nervous system and somatic gonad, two tissues that regulate adult longevity. We propose that DAF-12 integrates hormonal signals in cellular targets to coordinate major life history traits.
Alleles↗
Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans.
Males of the nematode Caenorhabditis elegans are shorter lived than hermaphrodites when maintained in single-sex groups. We observed that groups of young males form clumps and that solitary males live longer, indicating that male-male interactions reduce life span. By contrast, grouped or isolated hermaphrodites exhibited the same longevity. In one wild isolate of C. elegans, AB2, there was evidence of copulation between males. Nine uncoordinated (unc) mutations were used to block clumping behavior. These mutations had little effect on hermaphrodite life span in most cases, yet many increased male longevity even beyond that of solitary wild-type males. In one case, the neuronal function mutant unc-64(e246), hermaphrodite life span was also increased by up to 60%. The longevity of unc-4(e120), unc-13(e51), and unc-32(e189) males exceeded that of hermaphrodites by 70-120%. This difference appears to reflect a difference in sex-specific life span potential revealed in the absence of male behavior that is detrimental to survival. The greater longevity of males appears not to be affected by daf-2, but is influenced by daf-16. In the absence of male-male interactions, median (but not maximum) male life span was variable. This variability was reduced when dead bacteria were used as food. Maintenance on dead bacteria extended both male and hermaphrodite longevity.
Animals↗
Defining wild-type life span in Caenorhabditis elegans.
The nematode Caenorhabditis elegans reproduces predominantly as a self-fertilizing hermaphrodite, and this drives laboratory populations to be homozygous at all genetic loci. Passaging of stocks can lead to fixation of spontaneous mutations, especially when the latter do not result in a selective disadvantage under laboratory conditions. Life span may be such a trait, since a comparison of six wild-type N2 lines derived from a common ancestor (but maintained separately in several laboratories) revealed four variants with median adult life spans ranging from 12.0 +/- 0.8 to 17.0 +/- 0.6 days at 20 degrees C. Fertility was also reduced in the two shortest-lived strains. We determined which life span most closely corresponds to that of the authentic wild type by two means. Firstly, N2 hermaphrodites were compared with seven C. elegans wild isolates. The latter were found to resemble only the longest-lived N2 strain. Comparison of male life spans of six lines also revealed additional strain variation. Secondly, life spans of F1 progeny issuing from crosses between N2 variants showed that short life spans were recessive, indicating that they result from loss-of-function mutations. We infer that the longest-lived N2 variant best resembles the original N2 isolate. This is the N2 male stock currently distributed by the Caenorhabditis Genetics Center.
Aging↗
A Caenorhabditis elegans type I TGF beta receptor can function in the absence of type II kinase to promote larval development.
The daf-4 gene encodes a type II bone morphogenetic protein receptor in Caenorhabditis elegans that regulates dauer larva formation, body size and male tail patterning. The putative type I receptor partner for DAF-4 in regulating dauer larva formation is DAF-1. Genetic tests of the mechanism of activation of these receptors show that DAF-1 can signal in the absence of DAF-4 kinase activity. A daf-1 mutation enhances dauer formation in a daf-4 null background, whereas overexpression of daf-1 partially rescues a daf-4 mutant. DAF-1 alone cannot fully compensate for the loss of DAF-4 activity, indicating that nondauer development normally results from the activities of both receptors. DAF-1 signaling in the absence of a type II kinase is unique in the type I receptor family. The activity may be an evolutionary remnant, owing to daf-1's origin near the type I/type II divergence, or it may be an innovation that evolved in nematodes. daf-1 and daf-4 promoters both mediated expression of green fluorescent protein in the nervous system, indicating that a DAF-1/DAF-4 receptor complex may activate a neuronal signaling pathway. Signaling from a strong DAF-1/DAF-4 receptor complex or a weaker DAF-1 receptor alone may provide larvae with more precise control of the dauer/nondauer decision in a range of environmental conditions.
Activin Receptors, Type I↗
The relationship of lumbar flexion to disability in patients with low back pain.
BACKGROUND AND PURPOSE: Physical therapists routinely assess spinal active range of motion (AROM) in patients with low back pain (LBP). The purpose of this study was to use 2 approaches to examine the relationship between impairment of lumbar spine flexion AROM and disability. One approach relied on the use of normative data to determine when an impairment in flexion AROM was present. The other approach required therapists to make judgments of whether the flexion AROM impairment was relevant to the patient's disability. SUBJECTS: Fifteen physical therapists and 81 patients with LBP completed in the study. METHODS: Patients completed the Roland-Morris Back Pain Questionnaire (RMQ), and the therapists assessed lumbar spine flexion AROM using a dual-inclinometer technique at the initial visit and again at discharge. RESULTS: Correlations between the lumbar flexion AROM measure and disability were low and did not vary appreciably for the 2 approaches tested. CONCLUSION AND DISCUSSION: Measures of lumbar flexion AROM should not be used as surrogate measures of disability. Lumbar spine flexion AROM and disability are weakly correlated, suggesting that flexion AROM measures should not be used as treatment goals.
Adolescent↗
More expertise on trial.
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Clinical Competence↗
Ageing. A message from the gonads.
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Aging↗
The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network.
BACKGROUND AND PURPOSE: The purpose of this study was to assess the reliability, construct validity, and sensitivity to change of the Lower Extremity Functional Scale (LEFS). SUBJECTS AND METHODS: The LEFS was administered to 107 patients with lower-extremity musculoskeletal dysfunction referred to 12 outpatient physical therapy clinics. METHODS: The LEFS was administered during the initial assessment, 24 to 48 hours following the initial assessment, and then at weekly intervals for 4 weeks. The SF-36 (acute version) was administered during the initial assessment and at weekly intervals. A type 2,1 intraclass correlation coefficient was used to estimate test-retest reliability. Pearson correlations and one-way analyses of variance were used to examine construct validity. Spearman rank-order correlation coefficients were used to examine the relationship between an independent prognostic rating of change for each patient and change in the LEFS and SF-36 scores. RESULTS: Test-retest reliability of the LEFS scores was excellent (R = .94 [95% lower limit confidence interval (CI) = .89]). Correlations between the LEFS and the SF-36 physical function subscale and physical component score were r=.80 (95% lower limit CI = .73) and r = .64 (95% lower limit CI = .54), respectively. There was a higher correlation between the prognostic rating of change and the LEFS than between the prognostic rating of change and the SF-36 physical function score. The potential error associated with a score on the LEFS at a given point in time is +/-5.3 scale points (90% CI), the minimal detectable change is 9 scale points (90% CI), and the minimal clinically important difference is 9 scale points (90% CI). CONCLUSION AND DISCUSSION: The LEFS is reliable, and construct validity was supported by comparison with the SF-36. The sensitivity to change of the LEFS was superior to that of the SF-36 in this population. The LEFS is efficient to administer and score and is applicable for research purposes and clinical decision making for individual patients.
Activities of Daily Living↗
Interpreting validity indexes for diagnostic tests: an illustration using the Berg balance test.
Physical therapists routinely make diagnostic and prognostic decisions in the course of patient care. The purpose of this clinical perspective is to illustrate what we believe is the optimal method for interpreting the results of studies that describe the diagnostic or prognostic accuracy of examination procedures. To illustrate our points, we chose the Berg Balance Test as an exemplar measure. We combined the data from 2 previously published research reports designed to determine the validity of the Berg Balance Test for predicting risk of falls among elderly people. We calculated the most common validity indexes, including sensitivity, specificity, predictive values, and likelihood ratios for the combined data. Clinical scenarios were used to demonstrate how we believe these validity indexes should be used to guide clinical decisions. We believe therapists should use validity indexes to decrease the uncertainty associated with diagnostic and prognostic decisions. More studies of the accuracy of diagnostic and prognostic tests used by physical therapists are urgently needed.
Accidental Falls↗
Measurement of sacroiliac joint dysfunction: a multicenter intertester reliability study.
BACKGROUND AND PURPOSE: Previous research suggests that visual estimates of sacroiliac joint (SIJ) alignment are unreliable. The purpose of this study was to determine whether handheld calipers and an inclinometer could be used to obtain reliable measurements of SIJ alignment in subjects suspected of having SIJ dysfunction. SUBJECTS: Seventy-three subjects, evaluated at 1 of 5 outpatient clinics, participated in the study. METHODS: A total of 23 therapists, randomly paired for each subject, served as examiners. The angle of inclination of each innominate was measured while the subject was standing. The position of the innominates relative to each other was then derived. An intraclass correlation coefficient (ICC), the standard error of measurement (SEM), and a kappa coefficient were calculated to examine the reliability of the derived measurements. RESULTS: The ICC was .27, the SEM was 5.4 degrees, and the kappa value was .18. CONCLUSION AND DISCUSSION: Measurements of SIJ alignment were unreliable. Therapists should consider procedures other than those that assess SIJ alignment when evaluating the SIJ.
Adolescent↗
Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans.
The nematode Caenorhabditis elegans responds to overcrowding and scarcity of food by arresting development as a dauer larva, a nonfeeding, long-lived, stress-resistant, alternative third-larval stage. Previous work has shown that mutations in the genes daf-2 (encoding a member of the insulin receptor family) and age-1 (encoding a PI 3-kinase) result in constitutive formation of dauer larvae (Daf-c), increased adult longevity (Age), and increased intrinsic thermotolerance (Itt). Some daf-2 mutants have additional developmental, behavioral, and reproductive defects. We have characterized in detail 15 temperature-sensitive and 1 nonconditional daf-2 allele to investigate the extent of daf-2 mutant defects and to examine whether specific mutant traits correlate with each other. The greatest longevity seen in daf-2 mutant adults was approximately three times that of wild type. The temperature-sensitive daf-2 mutants fell into two overlapping classes, including eight class 1 mutants, which are Daf-c, Age, and Itt, and exhibit low levels of L1 arrest at 25.5 degrees. Seven class 2 mutants also exhibit the class 1 defects as well as some or all of the following: reduced adult motility, abnormal adult body and gonad morphology, high levels of embryonic and L1 arrest, production of progeny late in life, and reduced brood size. The strengths of the Daf-c, Age, and Itt phenotypes largely correlated with each other but not with the strength of class 2-specific defects. This suggests that the DAF-2 receptor is bifunctional. Examination of the null phenotype revealed a maternally rescued egg, L1 lethal component, and a nonconditional Daf-c component. With respect to the Daf-c phenotype, the dauer-defective (Daf-d) mutation daf-12(m20) was epistatic to daf-2 class 1 alleles but not the severe class 2 alleles tested. All daf-2 mutant defects were suppressed by the daf-d mutation daf-16(m26). Our findings suggest a new model for daf-2, age-1, daf-12, and daf-16 interactions.
Adaptation, Physiological↗
Sensitivity to change of the Roland-Morris Back Pain Questionnaire: part 1.
BACKGROUND AND PURPOSE: This study estimated the Roland-Morris Back Pain Questionnaire's (RMQ) change score that best classified patients as those who had achieved an important change and those who had not achieved an important change. The study also investigated whether the estimate of change was dependent on patients' initial scores. SUBJECTS AND METHODS: The RMQ was administered to 226 patients with low back pain of less than 6 weeks' duration during their initial visit for physical therapy and following 3 to 6 weeks of treatment. A global rating of change was used to classify patients as those who had changed an important amount and those who had not changed. Receiver operating characteristic curves were used to identify the RMQ change score that most accurately classified patients with respect to important change. This analysis was repeated for 5 overlapping subsamples of patients with initial scores 0 to 8, 5 to 12, 9 to 16, 13 to 20, and 17 to 24. RESULTS: The area under the receiver operating characteristic curves increased when patients' initial scores were taken into account. Estimates of important change were 2, 4, 5, 8, and 8 for the initial score intervals mentioned above. CONCLUSION AND DISCUSSION: Important change appears to be dependent on patients' initial RMQ scores. Subsequent inquiry using different hypotheses would add support to the estimates of important change found in this study.
Adolescent↗