Citations
All
Search in:AllTitleAbstractAuthor name
Publications
(3K+)
Patents
Grants
Pathways
Clinical trials
Publication
Journal: British Journal of Clinical Psychology
May/29/2007
Abstract
OBJECTIVE
To demonstrate the use of Rasch analysis by assessing the appropriateness of utilizing the Hospital Anxiety and Depression Scale (HADS) total score (HADS-14) as a measure of psychological distress.
METHODS
Cross-sectional, using Rasch analysis.
METHODS
The HADS was administered to 296 patients attending an out-patient musculoskeletal rehabilitation program. Rasch analysis was conducted using RUMM2020 software to assess the overall fit of the model, the response scale used, individual item fit, differential item functioning (DIF) and person separation.
RESULTS
Rasch analysis supported the viability of the HADS-14 as a measure of psychological distress. It showed good person separation, little disordering of the thresholds and no evidence of DIE One anxiety item (item 11) showed some misfit to the model. The residuals patterned into the two subscales (anxiety and depression), but the person estimate derived from these two subscales was not statistically different to that derived from all items taken together, supporting the assumption of unidimensionality. A cut-point of 12 on the HADS-14 identified all cases that were classified as both anxious and depressed on the original individual HADS subscales.
CONCLUSIONS
The results of Rasch analysis support the use of the HADS-14 as a global measure of psychological distress. The study demonstrates the usefulness of Rasch analysis in assessing the psychometric properties of a scale and suggests that further use of this technique to assess the HADS-14 in other clinical groups is warranted.
Publication
Journal: Journal of General Internal Medicine
September/10/2006
Abstract
OBJECTIVE
The Patient Health Questionnaire depression scale (PHQ-9) is a well-validated, Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) criterion-based measure for diagnosing depression, assessing severity and monitoring treatment response. The performance of most depression scales including the PHQ-9, however, has not been rigorously evaluated in different racial/ethnic populations. Therefore, we compared the factor structure of the PHQ-9 between different racial/ethnic groups as well as the rates of endorsement and differential item functioning (DIF) of the 9 items of the PHQ-9. The presence of DIF would indicate that responses to an individual item differ significantly between groups, controlling for the level of depression.
METHODS
A combined dataset from 2 separate studies of 5,053 primary care patients including non-Hispanic white (n=2,520), African American (n=598), Chinese American (n=941), and Latino (n=974) patients was used for our analysis. Exploratory principal components factor analysis was used to derive the factor structure of the PHQ-9 in each of the 4 racial/ethnic groups. A generalized Mantel-Haenszel statistic was used to test for DIF.
RESULTS
One main factor that included all PHQ-9 items was found in each racial/ethnic group with alpha coefficients ranging from 0.79 to 0.89. Although endorsement rates of individual items were generally similar among the 4 groups, evidence of DIF was found for some items.
CONCLUSIONS
Our analyses indicate that in African American, Chinese American, Latino, and non-Hispanic white patient groups the PHQ-9 measures a common concept of depression and can be effective for the detection and monitoring of depression in these diverse populations.
Publication
Journal: Pain
November/21/2010
Abstract
This paper describes the psychometric properties of the PROMIS-pain interference (PROMIS-PI) bank. An initial candidate item pool (n=644) was developed and evaluated based on the review of existing instruments, interviews with patients, and consultation with pain experts. From this pool, a candidate item bank of 56 items was selected and responses to the items were collected from large community and clinical samples. A total of 14,848 participants responded to all or a subset of candidate items. The responses were calibrated using an item response theory (IRT) model. A final 41-item bank was evaluated with respect to IRT assumptions, model fit, differential item function (DIF), precision, and construct and concurrent validity. Items of the revised bank had good fit to the IRT model (CFI and NNFI/TLI ranged from 0.974 to 0.997), and the data were strongly unidimensional (e.g., ratio of first and second eigenvalue=35). Nine items exhibited statistically significant DIF. However, adjusting for DIF had little practical impact on score estimates and the items were retained without modifying scoring. Scores provided substantial information across levels of pain; for scores in the T-score range 50-80, the reliability was equivalent to 0.96-0.99. Patterns of correlations with other health outcomes supported the construct validity of the item bank. The scores discriminated among persons with different numbers of chronic conditions, disabling conditions, levels of self-reported health, and pain intensity (p<0.0001). The results indicated that the PROMIS-PI items constitute a psychometrically sound bank. Computerized adaptive testing and short forms are available.
Publication
Journal: Scandinavian Journal of Public Health
January/17/2011
Abstract
OBJECTIVE
The aim of the present paper is to present the development of the second version of the Copenhagen Psychosocial Questionnaire (COPSOQ II).
METHODS
The development of COPSOQ II took place in five main steps: (1) We considered practical experience from the use of COPSOQ I, in particular feedback from workplace studies where the questionnaire had been used; (2) All scales concerning workplace factors in COPSOQ I were analyzed for differential item functioning (DIF) with regard to gender, age and occupational status; (3) A test version of COPSOQ II including new scales and items was developed and tested in a representative sample of working Danes between 20 and 59 years of age. In all, 3,517 Danish employees participated in the study. The overall response rate was 60.4%; (4) Based on psychometric analyses, the final questionnaire was developed; and (5) Criteria-related validity of the new scales was tested.
RESULTS
The development of COPSOQ II resulted in a questionnaire with 41 scales and 127 items. New scales on values at the workplace were introduced including scales on Trust, Justice and Social inclusiveness. Scales on Variation, Work pace, Recognition, Work-family conflicts and items on offensive behaviour were also added. New scales regarding health symptoms included: Burnout, Stress, Sleeping troubles and Depressive symptoms. In general, the new scales showed good criteria validity. All in all, 57% of the items of COPSOQ I were retained in COPSOQ II.
CONCLUSIONS
The COPSOQ I concept has been further developed and new validated scales have been included.
Publication
Journal: Genes and Development
February/24/2000
Abstract
We have revealed the subcellular localization of different DNA segments that are located at approximately 230-kb intervals on the Escherichia coli chromosome using fluorescence in situ hybridization (FISH). The series of chromosome segments is localized within the cell in the same order as the chromosome map. The large chromosome region including oriC shows similar localization patterns, which we call the Ori domain. In addition, the localization pattern of the large segment including dif is characteristic of the replication terminus region. The segment also shows similar localization patterns, which we call the Ter domain. In newborn cells, Ori and Ter domains of the chromosome are differentially localized near opposite cell poles. Subsequently, in the B period, the Ori domain moves toward mid-cell before the initiation of replication, and the Ter domain tends to relocate at mid-cell. An inversion mutant, in which the Ter domain is located close to oriC, shows abnormal subcellular localization of ori and dif segments, resulting in frequent production of anucleate cells. These studies thus suggest that the E. coli chromosome is organized to form a compacted ring structure with the Ori and Ter domains; these domains participate in the cell cycle-dependent localization of the chromosome.
Publication
Journal: Molecular Microbiology
April/28/2004
Abstract
The ability of a high frequency (10(-2)) of Escherichia coli to survive prolonged exposure to penicillin antibiotics, called high persistence, is associated with mutations in the hipA gene. The hip operon is located in the chromosomal terminus near dif and consists of two genes, hipA and hipB. The wild-type hipA gene encodes a toxin, whereas hipB encodes a DNA-binding protein that autoregulates expression of the hip operon and binds to HipA to nullify its toxic effects. We have characterized the hipA7 allele, which confers high persistence, and established that HipA7 is non-toxic, contains two mutations (G22S and D291A) and that both mutations are required for the full range of phenotypes associated with hip mutants. Furthermore, expression of hipA7 in the absence of hipB is sufficient to establish the high persistent phenotype, indicating that hipB is not required. There is a strong correlation between the frequency of persister cells generated by hipA7 strains and cell density, with hipA7 strains generating a 20-fold higher frequency of persisters as cultures approach stationary phase. It is also demonstrated that relA knock-outs diminish the high persistent phenotype in hipA7 mutants and that relA spoT knock-outs eliminate high persistence altogether, suggesting that hipA7 facilitates the establishment of the persister state by inducing (p)ppGpp synthesis. Consistent with this proposal, ectopic expression of relA' from a plasmid was shown to increase the number of persistent cells produced by hipA7 relA double mutants by 100-fold or more. A model is presented that postulates that hipA7 increases the basal level of (p)ppGpp synthesis, allowing a significantly greater percentage of cells in a population to assume a persistent, antibiotic-insensitive state by potentiating a rapid transition to a dormant state upon application of stress.
Publication
Journal: Cell
March/6/2002
Abstract
FtsK acts at the bacterial division septum to couple chromosome segregation with cell division. We demonstrate that a truncated FtsK derivative, FtsK(50C), uses ATP hydrolysis to translocate along duplex DNA as a multimer in vitro, consistent with FtsK having an in vivo role in pumping DNA through the closing division septum. FtsK(50C) also promotes a complete Xer recombination reaction between dif sites by switching the state of activity of the XerCD recombinases so that XerD makes the first pair of strand exchanges to form Holliday junctions that are then resolved by XerC. The reaction between directly repeated dif sites in circular DNA leads to the formation of uncatenated circles and is equivalent to the formation of chromosome monomers from dimers.
Publication
Journal: Molecular Microbiology
July/13/2005
Abstract
The process of DNA donation for natural transformation of bacteria is poorly understood and has been assumed to involve bacterial cell death. Recently in Neisseria gonorrhoeae we found that mutations in three genes in the gonococcal genetic island (GGI) reduced the ability of a strain to act as a donor in transformation and to release DNA into the culture. To better characterize the GGI and the process of DNA donation, the 57 kb genetic island was cloned, sequenced and subjected to insertional mutagenesis. DNA sequencing revealed that the GGI has characteristics of a horizontally acquired genomic island and encodes homologues of type IV secretion system proteins. The GGI was found to be incorporated near the chromosomal replication terminus at the dif site, a sequence targeted by the site-specific recombinase XerCD. Using a plasmid carrying a small region of the GGI and the associated dif site, we demonstrated that this model island could be integrated at the dif site in strains not carrying the GGI and was spontaneously excised from that site. Also, we were able to delete the entire 57 kb region by transformation with DNA from a strain lacking the GGI. Thus the GGI was likely acquired and integrated into the gonococcal chromosome by site-specific recombination and may be lost by site-specific recombination or natural transformation. We made mutations in six putative type IV secretion system genes and assayed these strains for the ability to secrete DNA. Five of the mutations greatly reduced or completely eliminated DNA secretion. Our data indicate that N. gonorrhoeae secretes DNA via a specific process. Donated DNA may be used in natural transformation, contributing to antigenic variation and the spread of antibiotic resistance, and it may modulate the host immune response.
Publication
Journal: Evaluation and the Health Professions
June/29/2005
Abstract
The FACIT (Functional Assessment of Chronic Illness Therapy) translation methodology has been in use for nearly 10 years and, during the course of that time, has emphasized a universal translation approach that includes multicountry review, the use of qualitative and quantitative methods in testing, and the exploration of new methods such as differential item functioning (DIF) analysis using item response theory to evaluate item equivalence. The FACIT translation methodology aims to establish equivalence of meaning and measurement between different country versions through the use of the decentered model of translation and advanced statistical methods.
Publication
Journal: Cell
December/28/1993
Abstract
There are striking parallels between the regulation of gene expression along the dorsoventral (DV) axis of Drosophila embryos and lymphoid-restricted expression in the mammalian immune system. Both depend on regulatory factors containing rel domains (dorsal and NF-kappa B) that are controlled at the level of nuclear transport. A novel Rel-containing gene in Drosophila, Dif (dorsal-related immunity factor), provides a potential link between these seemingly disparate processes. Although Dif maps close to dorsal, it does not appear to participate in DV patterning, but instead mediates an immune response in Drosophila larvae. Dif is normally localized in the cytoplasm of the larval fat body, but quickly accumulates in the nucleus upon bacterial infection or injury. Evidence is presented that once in the nucleus, Dif binds to kappa B-like sequence motifs present in promoter regions of immunity genes. These results suggest that mammalian and insect immunity share a common evolutionary origin.
Publication
Journal: Journal of Statistical Software
February/19/2017
Abstract
Logistic regression provides a flexible framework for detecting various types of differential item functioning (DIF). Previous efforts extended the framework by using item response theory (IRT) based trait scores, and by employing an iterative process using group-specific item parameters to account for DIF in the trait scores, analogous to purification approaches used in other DIF detection frameworks. The current investigation advances the technique by developing a computational platform integrating both statistical and IRT procedures into a single program. Furthermore, a Monte Carlo simulation approach was incorporated to derive empirical criteria for various DIF statistics and effect size measures. For purposes of illustration, the procedure was applied to data from a questionnaire of anxiety symptoms for detecting DIF associated with age from the Patient-Reported Outcomes Measurement Information System.
Publication
Journal: Immunity
June/19/2000
Abstract
We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals.
Publication
Journal: Cell
November/23/1993
Abstract
The stable inheritance of ColE1-related plasmids and the normal partition of the E. coli chromosome require the function of the Xer site-specific recombination system. We show that in addition to the XerC recombinase, whose function has already been implicated in this system, a second chromosomally encoded recombinase, XerD, is required. The XerC and XerD proteins show 37% identity and bind to separate halves of the recombination site. Both proteins act catalytically in the recombination reaction. Recombination site asymmetry and the requirement of two recombinases ensure that only correctly aligned sites are recombined. We predict that normal partition of most circular chromosomes requires the participation of site-specific recombination to convert any multimers (arising by homologous recombination) to monomers.
Publication
Journal: Gastroenterology
October/12/2011
Abstract
OBJECTIVE
Gastric cancer (GC) is a heterogeneous disease comprising multiple subtypes that have distinct biological properties and effects in patients. We sought to identify new, intrinsic subtypes of GC by gene expression analysis of a large panel of GC cell lines. We tested if these subtypes might be associated with differences in patient survival times and responses to various standard-of-care cytotoxic drugs.
METHODS
We analyzed gene expression profiles for 37 GC cell lines to identify intrinsic GC subtypes. These subtypes were validated in primary tumors from 521 patients in 4 independent cohorts, where the subtypes were determined by either expression profiling or subtype-specific immunohistochemical markers (LGALS4, CDH17). In vitro sensitivity to 3 chemotherapy drugs (5-fluorouracil, cisplatin, oxaliplatin) was also assessed.
RESULTS
Unsupervised cell line analysis identified 2 major intrinsic genomic subtypes (G-INT and G-DIF) that had distinct patterns of gene expression. The intrinsic subtypes, but not subtypes based on Lauren's histopathologic classification, were prognostic of survival, based on univariate and multivariate analysis in multiple patient cohorts. The G-INT cell lines were significantly more sensitive to 5-fluorouracil and oxaliplatin, but more resistant to cisplatin, than the G-DIF cell lines. In patients, intrinsic subtypes were associated with survival time following adjuvant, 5-fluorouracil-based therapy.
CONCLUSIONS
Intrinsic subtypes of GC, based on distinct patterns of expression, are associated with patient survival and response to chemotherapy. Classification of GC based on intrinsic subtypes might be used to determine prognosis and customize therapy.
Publication
Journal: Genes and Development
November/12/2000
Abstract
Here we report the identification of a Drosophila IkappaB kinase complex containing DmIKKbeta and DmIKKgamma, homologs of the human IKKbeta and IKKgamma proteins. We show that this complex is required for the signal-dependent cleavage of Relish, a member of the Rel family of transcriptional activator proteins, and for the activation of antibacterial immune response genes. In addition, we find that the activated DmIKK complex, as well as recombinant DmIKKbeta, can phosphorylate Relish in vitro. Thus, we propose that the Drosophila IkappaB kinase complex functions, at least in part, by inducing the proteolytic cleavage of Relish. The N terminus of Relish then translocates to the nucleus and activates the transcription of antibacterial immune response genes. Remarkably, this Drosophila IkappaB kinase complex is not required for the activation of the Rel proteins Dif and Dorsal through the Toll signaling pathway, which is essential for antifungal immunity and dorsoventral patterning during early development. Thus, a yet to be identified IkappaB kinase complex must be required for Rel protein activation via the Toll signaling pathway.
Publication
Journal: Value in Health
July/21/2009
Abstract
OBJECTIVE
This study assesses the reliability and validity of the European KIDSCREEN-52 generic health-related quality of life (HRQoL) questionnaire for children and adolescents.
METHODS
The KIDSCREEN-52, which measures HRQoL in 10 dimensions, was administered to a representative sample of 22,827 children and adolescents (8 to 18 years) in 13 European countries. Psychometric properties were assessed using the Classical Test Theory approach, Rasch analysis, and structural equation modeling (SEM). A priori expected associations between KIDSCREEN scales and sociodemographic and health-related factors were examined. Test-retest reliability was assessed in 10 countries.
RESULTS
For the overall sample, Cronbach's alpha values ranged from 0.77 to 0.89. Scaling success (Multitrait Analysis Program) was >97.8% for all dimensions and Rasch analysis item fit (INFITmsq) ranged from 0.80 to 1.27. The intraclass correlation coefficients ranged from 0.56 to 0.77. No sizeable differential item functioning (DIF) was found by age, sex or health status. Four items showed DIF across countries. The specified SEM fitted the data well (root mean square error of approximation: 0.06, comparative fit index: 0.98). Correlation coefficients between Pediatric Quality of Life Inventory, Child Health and Illness Profile-Adolescent Edition, and Youth Quality of Life Instrument scales and KIDSCREEN dimensions assessing similar constructs were moderate for those (r = 0.44 to 0.61). Statistically significant differences between children with and without physical and mental health problems (Children with Special Health Care Needs screener: d = 0.17 to 0.42, Strengths and Difficulties Questionnaire: d = 0.32 to 0.72) were found in all dimensions. All dimensions showed a gradient according to socioeconomic status.
CONCLUSIONS
The KIDSCREEN-52 questionnaire has acceptable levels of reliability and validity. Further work is needed to assess longitudinal validity and sensitivity to change.
Publication
Journal: Medical Care
February/22/2007
Abstract
BACKGROUND
We present an ordinal logistic regression model for identification of items with differential item functioning (DIF) and apply this model to a Mini-Mental State Examination (MMSE) dataset. We employ item response theory ability estimation in our models. Three nested ordinal logistic regression models are applied to each item. Model testing begins with examination of the statistical significance of the interaction term between ability and the group indicator, consistent with nonuniform DIF. Then we turn our attention to the coefficient of the ability term in models with and without the group term. If including the group term has a marked effect on that coefficient, we declare that it has uniform DIF. We examined DIF related to language of test administration in addition to self-reported race, Hispanic ethnicity, age, years of education, and sex.
METHODS
We used PARSCALE for IRT analyses and STATA for ordinal logistic regression approaches. We used an iterative technique for adjusting IRT ability estimates on the basis of DIF findings.
RESULTS
Five items were found to have DIF related to language. These same items also had DIF related to other covariates.
CONCLUSIONS
The ordinal logistic regression approach to DIF detection, when combined with IRT ability estimates, provides a reasonable alternative for DIF detection. There appear to be several items with significant DIF related to language of test administration in the MMSE. More attention needs to be paid to the specific criteria used to determine whether an item has DIF, not just the technique used to identify DIF.
Publication
Journal: Nature Immunology
April/18/2001
Abstract
We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.
Publication
Journal: Quality of Life Research
June/1/2011
Abstract
OBJECTIVE
The Patient-Reported Outcomes Measurement Information System (PROMIS) aims to develop self-reported item banks for clinical research. The PROMIS pediatrics (aged 8-17) project focuses on the development of item banks across several health domains (physical function, pain, fatigue, emotional distress, social role relationships, and asthma symptoms). The psychometric properties of the anxiety and depressive symptom item banks are described.
METHODS
Participants (n = 1,529) were recruited in public school settings, hospital-based outpatient and subspecialty pediatrics clinics. The anxiety (k = 18) and depressive symptoms (k = 21) items were split between two test administration forms. Hierarchical confirmatory factor-analytic models (CFA) were conducted to evaluate scale dimensionality and local dependence. IRT analyses were then used to finalize item banks and short forms.
RESULTS
CFA results confirmed that anxiety and depressive symptoms are separate constructs and indicative of negative affect. Items with local dependence and DIF were removed resulting in 15 anxiety and 14 depressive symptoms items. The psychometric differences between short forms and simulated computer adaptive tests are presented.
CONCLUSIONS
PROMIS pediatric item banks were developed to provide efficient assessment of health-related quality of life domains. This sample provides initial calibrations of anxiety and depressive symptoms item banks and creates PROMIS pediatric instruments, version 1.0.
Publication
Journal: Science
January/21/1990
Abstract
A protein secreted by cultured rat heart cells can direct the choice of neurotransmitter phenotype made by cultured rat sympathetic neurons. Structural analysis and biological assays demonstrated that this protein is identical to a protein that regulates the growth and differentiation of embryonic stem cells and myeloid cells, and that stimulates bone remodeling and acute-phase protein synthesis in hepatocytes. This protein has been termed D factor, DIA, DIF, DRF, HSFIII, and LIF. Thus, this cytokine, like IL-6 and TGF beta, regulates growth and differentiation in the embryo and in the adult in many tissues, now including the nervous system.
Publication
Journal: Genes and Development
May/12/1999
Abstract
The induction of immunity genes in Drosophila has been proposed to be dependent on Dorsal, Dif, and Relish, the NF-kappaB-related factors. Here we provide genetic evidence that Dif is required for the induction of only a subset of antimicrobial peptide genes. The results show that the presence of Dif without Dorsal is sufficient to mediate the induction of drosomycin and defensin. We also demonstrate that Dif is a downstream component of the Toll signaling pathway in activating the drosomycin expression. These results reveal that individual members of the NF-kappaB family in Drosophila have distinct roles in immunity and development.
Publication
Journal: EMBO Journal
December/12/2005
Abstract
Bacterial chromosomes are organized in replichores of opposite sequence polarity. This conserved feature suggests a role in chromosome dynamics. Indeed, sequence polarity controls resolution of chromosome dimers in Escherichia coli. Chromosome dimers form by homologous recombination between sister chromosomes. They are resolved by the combined action of two tyrosine recombinases, XerC and XerD, acting at a specific chromosomal site, dif, and a DNA translocase, FtsK, which is anchored at the division septum and sorts chromosomal DNA to daughter cells. Evidences suggest that DNA motifs oriented from the replication origin towards dif provide FtsK with the necessary information to faithfully distribute chromosomal DNA to either side of the septum, thereby bringing the dif sites together at the end of this process. However, the nature of the DNA motifs acting as FtsK orienting polar sequences (KOPS) was unknown. Using genetics, bioinformatics and biochemistry, we have identified a family of DNA motifs in the E. coli chromosome with KOPS activity.
Publication
Journal: The New biologist
November/24/1991
Abstract
XerC is a site-specific recombinase of the bacteriophage lambda integrase family that is encoded by xerC at 3700 kbp on the genetic map of Escherichia coli. The protein was originally identified through its role in converting multimers of plasmid ColE1 to monomers; only monomers are stably inherited. Here we demonstrate that XerC also has a role in the segregation of replicated chromosomes at cell division. xerC mutants form filaments with aberrant nucleotides that appear unable to partition correctly. A DNA segment (dif) from the replication terminus region of the E. coli chromosome binds XerC and acts as a substrate for XerC-mediated site-specific recombination when inserted into multicopy plasmids. This dif segment contains a region of 28 bp with sequence similarity to the crossover region of ColE1 cer. The cell division phenotype of xerC mutants is suppressed in strains deficient in homologous recombination, suggesting that the role of XerC/dif in chromosomal metabolism is to convert any chromosomal multimers (arising through homologous recombination) to monomers.
Publication
Journal: Nature
October/27/2004
Abstract
Most genes affect many traits. This phenomenon, known as pleiotropy, is a major constraint on evolution because adaptive change in one trait may be prevented because it would compromise other traits affected by the same genes. Here we show that pleiotropy can have an unexpected effect and benefit one of the most enigmatic of adaptations--cooperation. A spectacular act of cooperation occurs in the social amoeba Dictyostelium discoideum, in which some cells die to form a stalk that holds the other cells aloft as reproductive spores. We have identified a gene, dimA, in D. discoideum that has two contrasting effects. It is required to receive the signalling molecule DIF-1 that causes differentiation into prestalk cells. Ignoring DIF-1 and not becoming prestalk should allow cells to cheat by avoiding the stalk. However, we find that in aggregations containing the wild-type cells, lack of the dimA gene results in exclusion from spores. This pleiotropic linkage of stalk and spore formation limits the potential for cheating in D. discoideum because defecting on prestalk cell production results in an even greater reduction in spores. We propose that the evolution of pleiotropic links between cheating and personal costs can stabilize cooperative adaptations.
load more...