bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Father Care Mean Fathers Share?
Authors: Craig Lyn
Published: March 2006

This article uses diary data from the most recent Australian Bureau of Statistics Time Use Survey (N > 4,000) to compare by gender total child care time calculated in the measurements of (1) main activity, (2) main or secondary activity, and (3) total time spent in the company of children. It also offers an innovative gender comparison of relative time spent in (1) the activities that constitute child care, (2) child care as double activity, and (3) time with children in sole charge. These measures give a fuller picture of total time commitment to children and how men and women spend that time than has been available in previous time use analyses. The results indicate that compared to fathering, mothering involves not only more overall time commitment but more multitasking, more physical labor, a more rigid timetable, more time alone with children, and more overall responsibility for managing care. These gender differences in the quantity and nature of care apply even when women work full-time.
Understanding Variations in Media Coverage of U.S. Supreme Court Decisions
Authors: Haider-Markel Donald P. , Allen Mahalley D. , Johansen Morgen
Published: March 2006

Given the central importance of news media in providing the public with information about court decisions,this study examines variations in local and national media coverage of the Supreme Court decision on a Texas antisodomy law known as Lawrence v. Texas.The authors use content analysis of newspaper articles to test hypotheses concerning how media coverage of the case might vary by media outlet. The authors assess bias by examining overall coverage and the tone of coverage.The analysis suggests that media outlets varied in their coverage of the case,with states that had existing sodomy laws providing more coverage,and that some outlets tended to be more biased in their tone than others. The analysis confirms the importance of local relevance,but the authors also find that media outlet size and political context may play a role in determining coverage of an issue.
Negative News and the Sleeper Effect of Distrust
Authors: Kleinnijenhuis Jan , van Hoof Anita M. J. , Oegema Dirk
Published: March 2006

The role of the media in the creation of distrust is much debated in political communication. Will negative news, for example, relentless attacks on political authorities, result in political cynicism or in a stimulation effect? By and large the media may stimulate political participation,but it is less clear when negative news will nullify this effect. Negative news may not only have short-term behavioral effects but also effects on underlying attitudes such as trust in politicians, which may produce their “sleeper effect” on political behavior only in the long run. This article addresses two related research questions.Will negative news discourage trust in political leaders? Will trust have a sleeper effect for future party choice and future turnout within the months to come? The 2002 Dutch election campaign,being an unprecedented negative campaign as compared to other Dutch campaigns, provides a good case to investigate these questions. On the basis of a biweekly seven-wave panel survey study and a daily content analysis of television news and newspapers,negative news was found to have a significant effect on trust in party leaders in addition to prior vote preference and education.The distrust in party leaders also had a significant sleeper effect in the long run on turnout and on the actual vote in addition to previous intentions.In general,these findings support the malaise theory. They are helpful to explain why the Christian Democrats could win the elections in defiance of the polls.
The Role of Entertainment Television and Its Interactions with Individual Values in Explaining Political Participation
Authors: Besley John C.
Published: March 2006

This article highlights the potential for considering the interaction between media use and human values in discussions about traditional political participation. A model is presented that suggests entertainment television exposure is associated with decreased participation for most value types but that this impact is greatest on those who rate highest the progressive values of “self-transcendence” and “openness to change.” These relationships provide a context for the argument that entertainment television use is driving down political participation in Western countries. Data for ten European Union countries in the European Social Survey were used in the analyses.
A Muckraking Model
Authors: Feldstein Mark
Published: March 2006

Investigative reporting has long been considered a vital bulwark of democracy as a check on wrongdoing in politics and public policy. But a century after an American president coined a pejorative word to describe it—“muckraking”—exposé journalism has proved to be cyclical, waxing in some political periods and waning in others. While various studies have focused on the effects of investigative reporting, little scholarship has been written about its causes; and none has offered an overarching analysis that explains patterns of evolution over time. By using traditional historical methodology, this article traces the history of muckraking in America and proposes a unifying theory that explores its changes over the past two and a half centuries: a Muckraking Model based on supply and demand. This theory examines an important aspect of the intersection between press and politics and may have predictive value for the future as well as historical value about the past.
Perspective: A Review of Improved Ethical Practices in Environmental and Public Health Research: Case Examples From Native Communities
Authors: Quigley Dianne
Published: March 2006

This article presents a review of 14 case studies and articles of research ethics issues in the conduct of environmental and public health research with Native American and other indigenous populations. The purpose of this review is to highlight new practices in the ethical conduct of research with native community populations. The findings from this review can promote more dialogue and policy development on the issue of community protections in research. Formal guidelines exist in ethical codes for individual rights as human subjects, but there is a lack of development on community rights in the ethics of research. This review illustrates how communitybased participatory research practices can provide working guidelines that can overcome past research harms. More important, the compilations of guidelines offer tested field methods for improving the ethical conduct of research with native community populations.
Sustainability of the Prevention of Passive Infant Smoking Within Well-Baby Clinics
Authors: Crone M. R. , Verlaan M. , Willemsen M. C. , van Soelen P. , Reijneveld S. A. , Sing R. A. Hira , Paulussen T. G. W. M.
Published: March 2006

This study assessed the antecedents of continued use of an education program to prevent passive smoking in infants. It consists of a booklet for parents and a manual for health professionals describing a five-step procedure for discussing passive smoking. Aquestionnairewas sent to 67 managers, 670 nurses, and 335 physiciansworking in well-baby clinics (response rate: 70%, 53%, 47% respectively). Questions concerned the completeness of use, level of institutionalization, and characteristics of the organization, the user, and the dissemination strategy. Seventy-one percent of nurses and42% of physiciansworked with the program. They foremost provided the first three steps of the five-step procedure. Physicians' completeness of usewas related to their perceived responsibility in providing this education, and nurses' use was related to their perceived self-efficacy, responsibility, training attendance, participation in the adoption decision, and level of institutionalization. Diffusion efforts should focus on improving the completeness of use and level of institutionalization.
Anxiety's Relationship to Inconsistent Use of Oral Contraceptives
Authors: Walsemann Katrina M. , Perez Anthony Daniel
Published: March 2006

Five percent of typical oral contraceptive users experience an unintended pregnancy every year. Inconsistent use of oral contraception may be a leading contributor to the high rate of unintended pregnancy among oral contraceptive users. Previous medical research also suggests that anxiety may play a role in medication compliance, yet no known studies have examined the relationship between anxiety and oral contraceptive use. To test this relationship, the authors analyze data from the National Survey of Family Growth Cycle V (NSFG-V), restricting their sample to sexually activewomen currently taking oral contraceptives. They find thatwomenwho report multiple episodes of anxiety lasting at least 6 months have a greater probability of inconsistent use. The authors suggest goals for future research and discuss the role of health care professionals in addressing oral contraception compliance in light of their findings.
Opportunities for Student Physical Activity in Elementary Schools: A Cross-Sectional Survey of Frequency and Correlates
Authors: Barnett Tracie A. , O'Loughlin Jennifer , Gauvin Lise , Paradis Gilles , Hanley Jim
Published: March 2006

The objectives of this study were to describe opportunities for student physical activity (PA) in elementary schools and to identify factors in the school environment associated with higher PA opportunity. Self-report questionnaires were completed by school principals and physical education teachers in 277 schools (88% response) in metropolitan Montreal. Correlates of opportunity were identified using ordinal logistic regression. There was substantial variation in PA opportunities between schools. Higher opportunity was associated with role modeling of PA by school principals, their interest in increasing PA through links to the municipality, adequate financial and human resources, access to school sports facilities, adequate space for storing student sports equipment, and suburban location. There is both the need and the potential for intervention to increase PAopportunities in elementary schools. Addressing barriers related to resources and access to sports facilities may help reduce disparities between schools in opportunities for students to engage in PA.
Is Abstinence Education Theory Based? The Underlying Logic of Abstinence Education Programs in Texas
Authors: Goodson Patricia , Pruitt B. E. , Suther Sandy , Wilson Kelly , Buhi Eric
Published: March 2006

Authors examined the logic (or the implicit theory) underlying 16 abstinence-only-until-marriage programs in Texas (50% of all programs funded under the federal welfare reform legislation during 2001 and 2002). Defined as a set of propositions regarding the relationship between program activities and their intended outcomes, program staff's implicit theories were summarized and compared to (a) data from studies on adolescent sexual behavior, (b) a theory-based model of youth abstinent behavior, and (c) preliminary findings from the national evaluation of Title V programs. Authors interviewed 62 program directors and instructors and employed selected principles of grounded theory to analyze interview data. Findings indicated that abstinence education staff could clearly articulate the logic guiding program activity choices. Comparisons between interviewdata and a theory-based model of adolescent sexual behavior revealed striking similarities. Implications of these findings for conceptualizing and evaluating abstinence-only-until-marriage (or similar) programs are examined.
What (Not) to Expect When Surveying Executives
Authors: Cycyota Cynthia S. , Harrison David A.
Published: March 2006

The authors developed hypotheses about the effectiveness of response rate techniques for organizational researchers surveying executives. Using meta-analytic procedures to test those hypotheses, the authors analyzed response rate data from 231 studies that surveyed executives and appeared in top management journals from 1992 to 2003. They found mean response rates to be declining over the period, yielding an overall 32% rate. Of the various methods suggested to increase response rates in other populations, none were found to be effective for executives. However, topical salience and sponsorship by an organization or person in the executive's social networks did bring about response rate increases. The authors provide recommendations about what (not) to do when trying to collectoriginal data from members of a firm's upper echelons.
Bivariate Models of Fit in Contingency Theory
Authors: Meilich Ofer
Published: March 2006

The concept of fit in contingency theory has been modeled in ways that made it less conducive to detection. Each model of fit postulates a specific relationship between the structural, contingency, and outcome variables. Operationalization is then derived from this relationship. Conversely, a polynomial regression model would allow for a more generalized notion of fit while capturing the same forms of fit implied by existing models in a simpler, general, robust, and less constrained way.
A Tale of Two Methods
Authors: James Lawrence R. , Mulaik Stanley A. , Brett Jeanne M.
Published: March 2006

The structural equation modeling approach to testing for mediation is compared to the Baron and Kenny approach. The approaches are essentially the same when the hypothesis being tested predicts partial mediation. The approaches differ, however, in how each tests for complete mediation. Disparities in both theory and statistical estimators are identified and discussed. A strategy for future tests of mediation is recommended.
Conceptualizing Diversity and Leadership
Authors: Lumby Jacky
Published: March 2006

This article uses the theoretical framework of broad and narrow ways of conceptualizing diversity, the latter focusing primarily on those characteristics that are likely to lead to disadvantage, ethnicity, gender and disability, and the broader encompassing many more characteristics of ‘difference’, such as educational background, leadership style. It analyses evidence from 10 organizations in the Learning and Skills Sector in England to suggest that in most cases, while staff may be aware of the political dimension of narrower conceptualizations, they reject the latter as irrelevant or impractical, and certainly more problematic. Their orientation coverts ‘managing diversity’, derived from human resources theory, from its intended aim of increasing equity, to a conceptual sleight of hand for sidestepping uncomfortable issues. Staff are shown both to create an ‘other’ than the norm, an ‘outgroup’ particularly in relation to black and ethnic minority potential leaders, and to homogenize those who have entered leadership to delete any ‘other’. The article concludes by suggesting current leadership theory is complicit in underpinning the process of exclusion.
Inclusion, Diversity and Leadership
Authors: Leo Elizabeth , Barton Len
Published: March 2006

Drawing on research from a longitudinal case study of a large urban secondary school, this article examines senior leadership of and in a school struggling to be inclusive. The analysis focuses on the effect of senior leadership on: the ways in which inclusion is conceptualized and practised in this school, in particular by teachers; student intake profiles and diversity; teacher motivation and educational outcomes. The study illustrates how senior leaders are reconciling their commitment to moral values of inclusion and diversity to tackle disadvantage and underachievement, with the dominance of the Standards Agenda and associated pressures of short-term performance targets; the study also offers significant insights into the ways in which leadership conceptualizes and operationalizes contested concepts of inclusion and diversity. The article argues that simplistic distinctions between, for example, moral leadership, curriculum leadership, distributed leadership and other theories of leadership mask the multidimensional nature of leadership.
Adaptive functional differentiation of dendritic cells: integrating the network of extra- and intracellular signals
Authors: Luft Thomas , Rodionova Elena , Maraskovsky Eugene , Kirsch Michael , Hess Michael , Buchholtz Christian , Goerner Martin , Schnurr Max , Skoda Radek , Ho Anthony D.
Published: March 2006

Phenotypic maturation, cytokine secretion, and migration are distinct functional characteristics of dendritic cells (DCs). These functions are independently regulated by a number of extracellular variables, such as type, strength, and persistence of an array of soluble and membrane-bound mediators. Since the exact composition of these variables in response to infection may differ between individuals, the intracellular signaling pathways activated by these extracellular networks may more closely correlate with DC function and predict the course of adaptive immunity. We found that activation of p38 kinase (p38K), extracellular signal–related kinase 1/2 (ERK1/2), and phosphatidylcholine-specific phospholipase C (PC-PLC) enhanced cytokine secretion, whereas p38K, cyclic adenosine monophosphate (cAMP), and PC-PLC enhanced migration. In contrast, phosphatidylinositol 3-kinase (PI3K)/Akt-1 and cAMP inhibited cytokine secretion while ERK1/2 inhibited migration. Migration and cytokine secretion further differed in their sensitivity to inhibition over time. However, although DCs could be manipulated to express migration, cytokine secretion, or both, the level of activation or persistence of intracellular pathway signaling was not predictive. Our results suggest a modular organization of function. We hypothesize that the expression of specific DC functions integrates a large variety of activating and inhibitory variables, and is represented by the formation of a functional unit of molecular networks—the signal response module (SRM). The combined activities of these modules define the functional outcome of DC activation.
A balance between Raf-1 and Fas expression sets the pace of erythroid differentiation
Authors: Rubiolo Cristina , Piazzolla Daniela , Meissl Katrin , Beug Hartmut , Huber Johannes C. , Kolbus Andrea , Baccarini Manuela
Published: March 2006

Normal erythropoiesis critically depends on the balance between the renewal of precursor cells and their differentiation. If the renewal phase is shortened, the decrease in the precursor pool results in anemia; conversely, impaired differentiation increases the number of proliferating progenitors and the potential risk of leukemic transformation. Using gene ablation, we have discovered 2 self-sustaining signal transduction loops that antagonize each other and regulate erythroid progenitor proliferation and differentiation, respectively. We identify Raf-1 as the main activator of the MEK/ERK cascade and as the key molecule in maintaining progenitor proliferation. Differentiation, in contrast, is mediated by Fas via the activation of both the ASK1/JNK/p38 module and the caspase cascade. The point of convergence between the 2 cascades is activated ERK, which positively feeds back on the proliferation pathway by maintaining the expression of Raf-1, while inhibiting the expression of Fas and therefore differentiation. In turn, Fas, once expressed, antagonizes proliferation by exerting a negative feedback on ERK activation and Raf-1 expression. Simultaneously, Fas-mediated caspase activation precipitates differentiation. These results identify Raf-1 and Fas as the key molecules whose expression finely tunes erythropoiesis and the extent of ERK activation as the switch that tips the balance between them. (Blood. 2006;108:152-159)
Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo
Authors: Liu Ying , Pop Ramona , Sadegh Cameron , Brugnara Carlo , Haase Volker H. , Socolovsky Merav
Published: March 2006

Erythropoietin (Epo) is the principal regulator of the erythropoietic response to hypoxic stress, through its receptor, EpoR. The EpoR signals mediating the stress response are largely unknown, and the spectrum of progenitors that are stress responsive is not fully defined. Here, we used flow cytometry to identify stress-responsive Ter119+CD71highfschigh early erythroblast subsets in vivo. In the mouse spleen, an erythropoietic reserve organ, early erythroblasts were present at lower frequencies and were undergoing higher rates of apoptosis than equivalent cells in bone marrow. A high proportion of splenic early erythroblasts coexpressed the death receptor Fas, and its ligand, FasL. Fas-positive early erythroblasts were significantly more likely to coexpress annexin V than equivalent, Fas-negative cells, suggesting that Fas mediates early erythroblast apoptosis in vivo. We examined several mouse models of erythropoietic stress, including erythrocytosis and β-thalassemia. We found a dramatic increase in the frequency of splenic early erythroblasts that correlated with down-regulation of Fas and FasL from their cell surface. Further, a single injection of Epo specifically suppressed early erythroblast Fas and FasL mRNA and cell-surface expression. Therefore, Fas and FasL are negative regulators of erythropoiesis. Epo-mediated suppression of erythroblast Fas and FasL is a novel stress response pathway that facilitates erythroblast expansion in vivo. (Blood. 2006;108:123-133)
Patterns of autoimmunity and subsequent chronic lymphocytic leukemia in Nordic countries
Authors: Landgren Ola , Engels Eric A. , Caporaso Neil E. , Gridley Gloria , Mellemkjaer Lene , Hemminki Kari , Linet Martha S. , Goldin Lynn R.
Published: March 2006

A population-based case-control study was conducted to evaluate risk of developing chronic lymphocytic leukemia (CLL) associated with personal and/or family history of autoimmune and related diseases. Data were obtained for all (n = 7764) patients diagnosed with CLL in Sweden and Denmark over a 40-year period and with linkable relatives, 16 658 matched control subjects, and first-degree relatives of patients (n = 17 991) and control subjects (n = 39 388). Odds ratios (ORs) were calculated to quantify risk of CLL in relation to personal/family history of 32 autoimmune and related disorders. The risk of CLL was significantly increased among subjects with a personal history of pernicious anemia (OR = 1.94; 1.18-3.18), mainly in the 0- to 1-year latency period. A significantly decreased risk of CLL was found among individuals with a personal history of chronic rheumatic heart disease (OR = 0.55; 0.33-0.93), particularly persons with a long latency (10+ years) between the 2 conditions. We found no association between personal or familial occurrence of other autoimmune or related disorders and CLL. If our results are confirmed, mechanistic studies examining how pernicious anemia might promote increased occurrence of CLL and how chronic rheumatic heart disease protects against CLL, perhaps related to long-term antibiotics use, may provide insights to the as-yet-unknown etiology of CLL. (Blood. 2006;108:292-296)
Superior effects of high-dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2-center retrospective analysis
Authors: de Fost Maaike , Hollak Carla E. M. , Groener Johanna E. M. , Aerts Johannes M. F. G. , Maas Mario , Poll Ludger W. , Wiersma Maaike G. , Häussinger Dieter , Brett Sarah , Brill Nicole , Dahl Stephan vom
Published: March 2006

Dosing of enzyme replacement therapy (ERT) for Gaucher disease type 1 is still a subject of debate and varies from 15 to 130 U/kg/mo, making a huge economic difference of US $70 000 to US $380 000 (€55 000-300 000) per patient per year. To investigate whether this difference in dosing ultimately translates into a different response, we retrospectively compared long-term outcome of ERT at 2 large European treatment centers, Academic Medical Center, Amsterdam, The Netherlands (n = 49, median dose, 15-30 U/kg/4 wks) and Heinrich-Heine University, Duesseldorf, Germany (n = 57, median dose, 80 U/kg/4 wks). These adult cohorts had a similar genetic background. All follow-up parameters were matched separately at baseline, to avoid bias with respect to disease severity. Improvement in hemoglobin, platelet count, and hepatosplenomegaly was not significantly different between both cohorts, whereas plasma chitotriosidase and bone marrow involvement by magnetic resonance imaging improved more quickly and was more pronounced in the higher-dosed group. Major bone complications rarely occurred in both groups. In conclusion, different dosing regimens of ERT do not affect outcome of hematologic and visceral parameters, but higher dosing leads to accelerated decrease of chitotriosidase and better objective bone response in adult type 1 Gaucher disease.
Self-recognition is crucial for maintaining the peripheral CD4+ T-cell pool in a nonlymphopenic environment
Authors: Martin Bruno , Bécourt Chantal , Bienvenu Boris , Lucas Bruno
Published: March 2006

The role of self-recognition in the maintenance of the peripheral CD4+ T-cell pool has been extensively studied, but no clear answer has so far emerged. Indeed, in studies of the role of self-major histocompatibility complex (MHC) molecules in CD4+ T-cell survival, several parameters must be taken into account when interpreting the results: (1) in a lymphopenic environment, observations are biased by concomitant proliferation of T cells arising in MHC-expressing mice; (2) the peripheral T-cell compartment is qualitatively and quantitatively different in nonlymphopenic, normal, and MHC class II-deficient mice; and (3) in C57BL/6 Aβ-/- mice (traditionally considered MHC class II-deficient), the Aα chain and the Eβ chain associate to form a hybrid AαEβ MHC class II molecule. In light of these considerations, we revisited the role of interactions with MHC class II molecules in the survival of peripheral CD4+ T cells. We found that the answer to the question “is self-recognition required for CD4+ T cells to survive?” is not a simple yes or no. Indeed, although long-term survival of CD4+ T cells does not depend on self-recognition in lymphopenic mice, interactions with MHC class II molecules are required for maintaining the peripheral CD4+ T-cell pool in a nonlymphopenic environment. (Blood. 2006;108:270-277)
VEGF is upregulated by hypoxia-induced mitogenic factor via the PI-3K/Akt-NF-κB signaling pathway
Authors: Tong Qiangsong , Zheng Liduan , Lin Li , Li Bo , Wang Danming , Huang Chuanshu , Li Dechun
Published: March 2006

Background

Hypoxia-induced mitogenic factor (HIMF) is developmentally regulated and plays an important role in lung pathogenesis. We initially found that HIMF promotes vascular tubule formation in a matrigel plug model. In this study, we investigated the mechanisms which HIMF enhances expression of vascular endothelial growth factor (VEGF) in lung tissues and epithelial cells.

Methods

Recombinant HIMF protein was intratracheally instilled into adult mouse lungs, VEGF expression was examined by immunohistochemical staining and Western blot. The promoter-luciferase reporter assay, RT-PCR, and Western blot were performed to examine the effects of HIMF on VEGF expression in mouse lung epithelial cell line MLE-12. The activation of NF-kappa B (NF-κB) and phosphorylation of Akt, IKK and IκBα were examined by luciferase assay and Western blot, respectively.

Results

Intratracheal instillation of HIMF protein resulted in significant increase of VEGF, mainly localized to airway epithelial and alveolar type II cells. Deletion of NF-κB binding sites within VEGF promoter abolished HIMF-induced VEGF expression in MLE-12 cells, suggesting that activation of NF-κB is essential for VEGF upregulation induced by HIMF. Stimulation of lung epithelial cells by HIMF resulted in phosphorylation of IKK and IκBα, leading to activation of NF-κB. In addition, HIMF strongly induced Akt phosphorylation, and suppression of Akt activation by specific inhibitors and dominant negative mutants for PI-3K, and IKK or IκBα blocked HIMF-induced NF-κB activation and attenuated HIMF-induced VEGF production.

Conclusion

These results suggest that HIMF enhances VEGF production in mouse lung epithelial cells in a PI-3K/Akt-NF-κB signaling pathway-dependent manner, and may play critical roles in pulmonary angiogenesis.
Farnesylation or geranylgeranylation? Efficient assays for testing protein prenylation in vitro and in vivo
Authors: Benetka Wolfgang , Koranda Manfred , Maurer-Stroh Sebastian , Pittner Fritz , Eisenhaber Frank
Published: March 2006

Background

Available in vitro and in vivo methods for verifying protein substrates for posttranslational modifications via farnesylation or geranylgeranylation (for example, autoradiography with 3H-labeled anchor precursors) are time consuming (weeks/months), laborious and suffer from low sensitivity.

Results

We describe a new technique for detecting prenyl anchors in N-terminally glutathione S-transferase (GST)-labeled constructs of target proteins expressed in vitro in rabbit reticulocyte lysate and incubated with 3H-labeled anchor precursors. Alternatively, hemagglutinin (HA)-labeled constructs expressed in vivo (in cell culture) can be used. For registration of the radioactive marker, we propose to use a thin layer chromatography (TLC) analyzer. As a control, the protein yield is tested by Western blotting with anti-GST- (or anti-HA-) antibodies on the same membrane that has been previously used for TLC-scanning. These protocols have been tested with Rap2A, v-Ki-Ras2 and RhoA (variant RhoA63L) including the necessary controls. We show directly that RasD2 is a farnesylation target.

Conclusion

Savings in time for experimentation and the higher sensitivity for detecting 3H-labeled lipid anchors recommend the TLC-scanning method with purified GST- (or HA-) tagged target proteins as the method of choice for analyzing their prenylation capabilities in vitro and in vivo and, possibly, also for studying the myristoyl and palmitoyl posttranslational modifications.
The protein kinase DYRK1A phosphorylates the splicing factor SF3b1/SAP155 at Thr434, a novel in vivo phosphorylation site
Authors: de Graaf Katrin , Czajkowska Hanna , Rottmann Sabine , Packman Len C , Lilischkis Richard , Lüscher Bernhard , Becker Walter
Published: March 2006

Background

The U2 small nuclear ribonucleoprotein particle (snRNP) component SF3b1/SAP155 is the only spliceosomal protein known to be phosphorylated concomitant with splicing catalysis. DYRK1A is a nuclear protein kinase that has been localized to the splicing factor compartment. Here we describe the identification of DYRK1A as a protein kinase that phosphorylates SF3b1 in vitro and in cultivated cells.

Results

Overexpression of DYRK1A caused a markedly increased phosphorylation of SF3b1 in COS-7 cells as assessed by Western blotting with an antibody specific for phosphorylated Thr-Pro dipeptide motifs. Phosphopeptide mapping of metabolically labelled SF3b1 showed that the majority of the in vivo-phosphopeptides corresponded to sites also phosphorylated by DYRK1A in vitro. Phosphorylation with cyclin E/CDK2, a kinase previously reported to phosphorylate SF3b1, generated a completely different pattern of phosphopeptides. By mass spectrometry and mutational analysis of SF3b1, Thr434 was identified as the major phosphorylation site for DYRK1A. Overexpression of DYRK1A or the related kinase, DYRK1B, resulted in an enhanced phosphorylation of Thr434 in endogenous SF3b1 in COS-7 cells. Downregulation of DYRK1A in HEK293 cells or in HepG2 cells by RNA interference reduced the phosphorylation of Thr434 in SF3b1.

Conclusion

The present data show that the splicing factor SF3b1 is a substrate of the protein kinase DYRK1A and suggest that DYRK1A may be involved in the regulation of pre mRNA-splicing.
Methodological study of affine transformations of gene expression data with proposed robust non-parametric multi-dimensional normalization method
Authors: Bengtsson Henrik , Hössjer Ola
Published: March 2006

Background

Low-level processing and normalization of microarray data are most important steps in microarray analysis, which have profound impact on downstream analysis. Multiple methods have been suggested to date, but it is not clear which is the best. It is therefore important to further study the different normalization methods in detail and the nature of microarray data in general.

Results

A methodological study of affine models for gene expression data is carried out. Focus is on two-channel comparative studies, but the findings generalize also to single- and multi-channel data. The discussion applies to spotted as well as in-situ synthesized microarray data. Existing normalization methods such as curve-fit ("lowess") normalization, parallel and perpendicular translation normalization, and quantile normalization, but also dye-swap normalization are revisited in the light of the affine model and their strengths and weaknesses are investigated in this context. As a direct result from this study, we propose a robust non-parametric multi-dimensional affine normalization method, which can be applied to any number of microarrays with any number of channels either individually or all at once. A high-quality cDNA microarray data set with spike-in controls is used to demonstrate the power of the affine model and the proposed normalization method.

Conclusion

We find that an affine model can explain non-linear intensity-dependent systematic effects in observed log-ratios. Affine normalization removes such artifacts for non-differentially expressed genes and assures that symmetry between negative and positive log-ratios is obtained, which is fundamental when identifying differentially expressed genes. In addition, affine normalization makes the empirical distributions in different channels more equal, which is the purpose of quantile normalization, and may also explain why dye-swap normalization works or fails. All methods are made available in the aroma package, which is a platform-independent package for R.
SinicView: A visualization environment for comparisons of multiple nucleotide sequence alignment tools
Authors: Shih Arthur Chun-Chieh , Lee DT , Lin Laurent , Peng Chin-Lin , Chen Shiang-Heng , Wu Yu-Wei , Wong Chun-Yi , Chou Meng-Yuan , Shiao Tze-Chang , Hsieh Mu-Fen
Published: March 2006

Background

Deluged by the rate and complexity of completed genomic sequences, the need to align longer sequences becomes more urgent, and many more tools have thus been developed. In the initial stage of genomic sequence analysis, a biologist is usually faced with the questions of how to choose the best tool to align sequences of interest and how to analyze and visualize the alignment results, and then with the question of whether poorly aligned regions produced by the tool are indeed not homologous or are just results due to inappropriate alignment tools or scoring systems used. Although several systematic evaluations of multiple sequence alignment (MSA) programs have been proposed, they may not provide a standard-bearer for most biologists because those poorly aligned regions in these evaluations are never discussed. Thus, a tool that allows cross comparison of the alignment results obtained by different tools simultaneously could help a biologist evaluate their correctness and accuracy.

Results

In this paper, we present a versatile alignment visualization system, called SinicView, (for Sequence-aligning INnovative and Interactive Comparison VIEWer), which allows the user to efficiently compare and evaluate assorted nucleotide alignment results obtained by different tools. SinicView calculates similarity of the alignment outputs under a fixed window using the sum-of-pairs method and provides scoring profiles of each set of aligned sequences. The user can visually compare alignment results either in graphic scoring profiles or in plain text format of the aligned nucleotides along with the annotations information. We illustrate the capabilities of our visualization system by comparing alignment results obtained by MLAGAN, MAVID, and MULTIZ, respectively.

Conclusion

With SinicView, users can use their own data sequences to compare various alignment tools or scoring systems and select the most suitable one to perform alignment in the initial stage of sequence analysis.
SCOWLP: a web-based database for detailed characterization and visualization of protein interfaces
Authors: Teyra Joan , Doms Andreas , Schroeder Michael , Pisabarro M Teresa
Published: March 2006

Background

Currently there is a strong need for methods that help to obtain an accurate description of protein interfaces in order to be able to understand the principles that govern molecular recognition and protein function. Many of the recent efforts to computationally identify and characterize protein networks extract protein interaction information at atomic resolution from the PDB. However, they pay none or little attention to small protein ligands and solvent. They are key components and mediators of protein interactions and fundamental for a complete description of protein interfaces. Interactome profiling requires the development of computational tools to extract and analyze protein-protein, protein-ligand and detailed solvent interaction information from the PDB in an automatic and comparative fashion. Adding this information to the existing one on protein-protein interactions will allow us to better understand protein interaction networks and protein function.

Description

SCOWLP (S tructural C haracterization O f W ater, L igands and P roteins) is a user-friendly and publicly accessible web-based relational database for detailed characterization and visualization of the PDB protein interfaces. The SCOWLP database includes proteins, peptidic-ligands and interface water molecules as descriptors of protein interfaces. It contains currently 74,907 protein interfaces and 2,093,976 residue-residue interactions formed by 60,664 structural units (protein domains and peptidic-ligands) and their interacting solvent.

The SCOWLP web-server allows detailed structural analysis and comparisons of protein interfaces at atomic level by text query of PDB codes and/or by navigating a SCOP-based tree. It includes a visualization tool to interactively display the interfaces and label interacting residues and interface solvent by atomic physicochemical properties. SCOWLP is automatically updated with every SCOP release.

Conclusion

SCOWLP enriches substantially the description of protein interfaces by adding detailed interface information of peptidic-ligands and solvent to the existing protein-protein interaction databases. SCOWLP may be of interest to many structural bioinformaticians. It provides a platform for automatic global mapping of protein interfaces at atomic level, representing a useful tool for classification of protein interfaces, protein binding comparative studies, reconstruction of protein complexes and understanding protein networks. The web-server with the database and its additional summary tables used for our analysis are available at http://www.scowlp.org.
A quantitative analysis of secondary RNA structure using domination based parameters on trees
Authors: Haynes Teresa , Knisley Debra , Seier Edith , Zou Yue
Published: March 2006

Background

It has become increasingly apparent that a comprehensive database of RNA motifs is essential in order to achieve new goals in genomic and proteomic research. Secondary RNA structures have frequently been represented by various modeling methods as graph-theoretic trees. Using graph theory as a modeling tool allows the vast resources of graphical invariants to be utilized to numerically identify secondary RNA motifs. The domination number of a graph is a graphical invariant that is sensitive to even a slight change in the structure of a tree. The invariants selected in this study are variations of the domination number of a graph. These graphical invariants are partitioned into two classes, and we define two parameters based on each of these classes. These parameters are calculated for all small order trees and a statistical analysis of the resulting data is conducted to determine if the values of these parameters can be utilized to identify which trees of orders seven and eight are RNA-like in structure.

Results

The statistical analysis shows that the domination based parameters correctly distinguish between the trees that represent native structures and those that are not likely candidates to represent RNA. Some of the trees previously identified as candidate structures are found to be "very" RNA like, while others are not, thereby refining the space of structures likely to be found as representing secondary RNA structure.

Conclusion

Search algorithms are available that mine nucleotide sequence databases. However, the number of motifs identified can be quite large, making a further search for similar motif computationally difficult. Much of the work in the bioinformatics arena is toward the development of better algorithms to address the computational problem. This work, on the other hand, uses mathematical descriptors to more clearly characterize the RNA motifs and thereby reduce the corresponding search space. These preliminary findings demonstrate that graph-theoretic quantifiers utilized in fields such as computer network design hold significant promise as an added tool for genomics and proteomics.
IsoSVM – Distinguishing isoforms and paralogs on the protein level
Authors: Spitzer Michael , Lorkowski Stefan , Cullen Paul , Sczyrba Alexander , Fuellen Georg
Published: March 2006

Background

Recent progress in cDNA and EST sequencing is yielding a deluge of sequence data. Like database search results and proteome databases, this data gives rise to inferred protein sequences without ready access to the underlying genomic data. Analysis of this information (e.g. for EST clustering or phylogenetic reconstruction from proteome data) is hampered because it is not known if two protein sequences are isoforms (splice variants) or not (i.e. paralogs/orthologs). However, even without knowing the intron/exon structure, visual analysis of the pattern of similarity across the alignment of the two protein sequences is usually helpful since paralogs and orthologs feature substitutions with respect to each other, as opposed to isoforms, which do not.

Results

The IsoSVM tool introduces an automated approach to identifying isoforms on the protein level using a support vector machine (SVM) classifier. Based on three specific features used as input of the SVM classifier, it is possible to automatically identify isoforms with little effort and with an accuracy of more than 97%. We show that the SVM is superior to a radial basis function network and to a linear classifier. As an example application we use IsoSVM to estimate that a set ofXenopus laevisEST clusters consists of approximately 81% cases where sequences are each other's paralogs and 19% cases where sequences are each other's isoforms. The number of isoforms and paralogs in this allotetraploid species is of interest in the study of evolution.

Conclusion

We developed an SVM classifier that can be used to distinguish isoforms from paralogs with high accuracy and without access to the genomic data. It can be used to analyze, for example, EST data and database search results. Our software is freely available on the Web, under the name IsoSVM.
Lower expression of genes near microRNA in C. elegans germline
Authors: Inaoka Hidenori , Fukuoka Yutaka , Kohane Isaac S
Published: March 2006

Background

MicroRNAs (miRNAs) are recently discovered short non-protein-coding RNA molecules. miRNAs are increasingly implicated in tissue-specific transcriptional control and particularly in development. Because there is mounting evidence for the localized component of transcriptional control, we investigated if there is a distance-dependent effect of miRNA.

Results

We analyzed gene expression levels around the 84 of 113 know miRNAs for which there are nearby gene that were measured in the data in two independent C. elegans expression data sets. The expression levels are lower for genes in the vicinity of 59 of 84 (71%) miRNAs as compared to genes far from such miRNAs. Analysis of the genes with lower expression in proximity to the miRNAs reveals increased frequency matching of the 7 nucleotide "seed"s of these miRNAs.

Conclusion

We found decreased messenger RNA (mRNA) abundance, localized within a 10 kb of chromosomal distance of some miRNAs, in C. elegans germline. The increased frequency of seed matching near miRNA can explain, in part, the localized effects.
MAGIC-SPP: a database-driven DNA sequence processing package with associated management tools
Authors: Liang Chun , Sun Feng , Wang Haiming , Qu Junfeng , Freeman Robert M , Pratt Lee H , Cordonnier-Pratt Marie-Michèle
Published: March 2006

Background

Processing raw DNA sequence data is an especially challenging task for relatively small laboratories and core facilities that produce as many as 5000 or more DNA sequences per week from multiple projects in widely differing species. To meet this challenge, we have developed the flexible, scalable, and automated sequence processing package described here.

Results

MAGIC-SPP is a DNA sequence processing package consisting of an Oracle 9i relational database, a Perl pipeline, and user interfaces implemented either as JavaServer Pages (JSP) or as a Java graphical user interface (GUI). The database not only serves as a data repository, but also controls processing of trace files. MAGIC-SPP includes an administrative interface, a laboratory information management system, and interfaces for exploring sequences, monitoring quality control, and troubleshooting problems related to sequencing activities. In the sequence trimming algorithm it employs new features designed to improve performance with respect to concerns such as concatenated linkers, identification of the expected start position of a vector insert, and extending the useful length of trimmed sequences by bridging short regions of low quality when the following high quality segment is sufficiently long to justify doing so.

Conclusion

MAGIC-SPP has been designed to minimize human error, while simultaneously being robust, versatile, flexible and automated. It offers a unique combination of features that permit administration by a biologist with little or no informatics background. It is well suited to both individual research programs and core facilities.