bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative Donor Sources in Pediatric Bone Marrow Transplantation
Authors: Forte Katherine J.
Published: July 2007

Every year 2,800 children are diagnosed with leukemia and between 30% and 60% will relapse and need a bone marrow transplant. In addition, children with hematologic, genetic, or immunologic diseases may also require a transplant to be cured. Unfortunately, only 30% of these children will have a human leukocyte antigen-matched sibling donor. The current options for alternative donor sources include matched unrelated donor, mismatched related donor, and unrelated cord blood donor. Compared to a matched sibling donor, each of these options has an increased risk for graft failure and graft-versus-host disease (GVHD). For patients who receive stem cells from matched unrelated donors or mismatched related donors, the risk of graft failure is 5% to 10% and the risk of GVHD approaches 80%. After unrelated cord blood transplants, the graft failure rate is 8%, but this is potentially offset by less severe GVHD. Challenges for nurses include providing anticipatory guidance for patients and families undergoing these novel therapies and devising treatment strategies to manage the complications. Graft failure, GVHD, and infections pose the most significant risks associated with alternative donor transplants.
Bone Marrow Transplant Today—Home Tomorrow: Ambulatory Care Issues in Pediatric Marrow Transplantation
Authors: Fidler Patricia A. , Hibbs Cynthia J.
Published: July 2007

Pediatric marrow transplantation is now an accepted and increasingly successful intensive therapy for a wide range of disorders in children. Supportive therapies that were once thought to be possible only in the acute care setting can now be safely managed in the outpatient arena. This shift is influenced by scientific and patient care advances and by managed care and cost containment trends. The purpose of this article is to examine the interrelated aspects of change in health care delivery and their impact on pediatric bone marrow transplant recipients and families. Nurses working in all aspects of pediatric marrow transplantation have an opportunity and responsibility to impact quality patient care in the outpatient setting.
Impedance-Based Modeling of Actuators Bonded to Shell Structures
Authors: Lalande F. , Chaudhry Z. , Rogers C.A.
Published: July 2007

When discrete piezoelectric actuator patches bonded on structures are used for active shape, vibration, and acoustic control, the desired deformation field in the structure is obtained through the application of localized line forces and moments generated by expanding or contracting bonded piezoelectric actuators. An impedance-based model to predict the dynamic response of cylindrical shells subjected to excitation from surface-bonded induced strain actuators is presented. The essence of the impedance approach is to match the actuator impedance with the structural impedance at the ends of the actuators, which will retain the dynamic characteristics of the actuators. A detailed derivation of the actuator and structural impedance is included. It is found that the actuator's output dynamic force in the axial and tangential direction are not equal. Various case studies of a cylindrical thin shell are performed to illustrate the capabilities of the developed impedance model. Out-of-phase actuation is shown to be the most efficient in exciting the lower order bending modes of shell structures. The paper is concluded with a finite element analysis verification of the derived impedance model.
Zig-Zag Piezoelectric Actuators: Geometrical Control of Displacement and Resonance
Authors: Matsko M.G. , Xu Q.C. , Newnham R.E.
Published: July 2007

The Zig-Zag actuator is a hybrid design combining bimorph and multilayer characteristics that is capable of producing and sensing usable motion in two dimensions. The mechanical impedance can be optimized by changing the angle between the legs and the actuator's working parameters controlled by changing the driving voltage and its frequency. Two interesting features of this actuator are its performance as a linear motor and its ability to drive a load in two directions.
An Isolated Structural System Using Localized Vibration Control
Authors: Hannsen Su J. , Ruckman C.E.
Published: July 2007

This paper describes an approach to actively isolate vibration of a complex structural system by controlling six degrees of freedom in its support areas. The controller attempts to stabilize only localized areas near where the structure is supported rather than attempting to stabilize the entire structure. Actuator/sensor placement and model reduction are discussed, and the specific controller design and performance measure are described. The relative performance levels of different control strategies are evaluated by examining a frequency-dependent disturbance rejection property. Concepts are illustrated by numerically simulating a complex structural system comprising a flat plate supported by two box girders; plant dynamics are obtained from a finite-element model. Conclusions are drawn regarding the mechanisms by which localized vibration control is exerted.
Martensitic Transformations in a NiTi Fiber Reinforced 6061 Aluminum Matrix Composite
Authors: Armstrong William D. , Kino Hironori
Published: July 2007

Approximately 19.5 volume percent, 50.7 at % Ni-Ti shape memory alloy fiber reinforced 6061-T6 aluminum alloy matrix composite (SMA-MMC) and homogeneous 6061-T6 control materials were produced by vacuum hot pressing. The test materials were initially subjected to a 5.8% tensile elongation at room temperature. During this process, the shape memory alloy reinforced composite materials exhibited a bimodal yield. The initial yield was due to plastic flow in the aluminum matrix, the subsequent yield was due to the initiation of a stress induced austenite to martensite (SIM) transformation in the shape memory alloy fibers. The SMA-MMC specimens exhibited unusual positive curvature hardening during the final stages of the 25°C tensile loading resulting from the saturation of the SIM transformation. During the subsequent 25 °C to 75 °C unconstrained heating process, the SMA-MMC exhibited a nonlinear thermal contraction resulting from the martensite to austenite shape memory transformation of the NiTi reinforcement. At the conclusion of the unconstrained heating process the temperature was held constant at 75°C as the loading grips were reapplied and the test materials were tensile loaded to failure. The elevated temperature flow strength of the SMA-MMC was significantly higher than the final SMA-MMC room temperature flow strength; this increase was due to the imposition of a large longitudinal compressive stress in the composite matrix by the NiTi fiber shape memory response, and due to the increase in NiTi fiber transformation stress with increased temperature. The elevated temperature ultimate strength and final failure strain of the SMA-MMC materials were both significantly higher than that of the 6061-T6 control materials. The experimental results are analyzed by a nonlinear, one-dimensional composite constitutive model. The model provides a compact quantitative description of the SMA-MMC thermal mechanical response as a function of temperature and applied stress, and correctly expresses important experimental features.
The Magnetoviscoelastic Response of Elastomer Composites Consisting of Ferrous Particles Embedded in a Polymer Matrix
Authors: Jolly Mark R. , Carlson J. David , Muñoz Beth C. , Bullions Todd A.
Published: July 2007

The mechanical response of elastomer composites to applied magnetic fields is examined. These elastomer composites consist of carbonyl iron particles embedded within a molded elastomer matrix. The composite is subjected to a strong magnetic field during curing, which causes the iron particles to form columnar structures that are parallel to the applied field. This special composite geometry is known to enhance the mechanical response to the application of post-cured magnetic fields. Experimental data is presented that shows that up to a 0.6 MPa change in mechanical shear modulus (which represents 30-40% change in modulus for the materials tested) is possible in response to an applied magnetic field for a composite containing 30% (V/V) iron particles. A simple quasi-static dipole model is presented to examine the magnetoviscoelastic effect of these elastomer composites. The model is semi-empirical in that it may be fit to experimental data over a broad range of applied fields by adjusting a parameter that accounts for unmodeled multipolar magnetic interactions between particles within the composite. Such elastomer composites hold promise in enabling variable stiffness devices and adaptive structures.
Estimating Effect Sizes From Pretest-Posttest-Control Group Designs
Authors: Morris Scott B.
Published: July 2007

Previous research has recommended several measures of effect size for studies with repeated measurements in both treatment and control groups. Three alternate effect size estimates were compared in terms of bias, precision, and robustness to heterogeneity of variance. The results favored an effect size based on the mean pre-post change in the treatment group minus the mean pre-post change in the control group, divided by the pooled pretest standard deviation.
Comparison of Three Meta-Analytic Procedures for Estimating Moderating Effects of Categorical Variables
Authors: Aguinis Herman , Sturman Michael C. , Pierce Charles A.
Published: July 2007

The authors conducted Monte Carlo simulations to compare the Hedges and Olkin, the Hunter and Schmidt, and a refinement of the Aguinis and Pierce meta-analytic approaches for estimating moderating effects of categorical variables. The simulation examined binary moderator variables (e.g., gender—male, female; ethnicity—majority, minority). The authors compared the three meta-analytic methods in terms of their point estimation accuracy and Type I and Type II error rates. Results provide guidelines to help researchers choose among the three meta-analytic techniques based on theory (i.e., exploratory vs. confirmatory research) and research design considerations (i.e., degree of range restriction and measurement error).
Improved Shrinkage Estimation of Squared Multiple Correlation Coefficient and Squared Cross-Validity Coefficient
Authors: Shieh Gwowen
Published: July 2007

The sample squared multiple correlation coefficient is widely used for describing the usefulness of a multiple linear regression model in many areas of science. In this article, the author considers the problem of estimating the squared multiple correlation coefficient and the squared cross-validity coefficient under the assumption that the response and predictor variables have a joint multinormal distribution. Detailed numerical investigations are conducted to assess the exact bias and mean square error of the proposed modifications of established estimators. Notably, the positive-part Pratt estimator and the synthesis of Browne and positive-part Pratt estimators are recommended in the estimation of squared multiple correlation coefficient and squared cross-validity coefficient, respectively, for their overall advantages of incurring the least amount of statistical discrepancy and computational requirement.
Does the Measure of Dispersion Matter in Multilevel Research? A Comparison of the Relative Performance of Dispersion Indexes
Authors: Roberson Quinetta M. , Sturman Michael C. , Simons Tony L.
Published: July 2007

Within the context of climate strength, this simulation study examines the validity of various dispersion indexes for detecting meaningful relationships between variability in group member perceptions and outcome variables. We used the simulation to model both individual-and group-level phenomena, vary appropriate population characteristics, and test the proclivity of standard and average deviation, interrater agreement indexes (rwg, r*wg, awg), and coefficient of variation (both normed and unnormed) for Type I and Type II errors. The results show that the coefficient of variation was less likely to detect interaction effects although it outperformed other measures when detecting level effects. Standard deviation was shown to be inferior to other indexes when no level effect is present although it may be an effective measure of dispersion when modeling strength or interaction effects. The implications for future research, in which dispersion is a critical component of the theoretical model, are discussed.
On the Use of Likert-Type Scales in Multilevel Data
Authors: Beal Daniel J. , Dawson Jeremy F.
Published: July 2007

In multilevel analyses, problems may arise when using Likert-type scales at the lowest level of analysis. Specifically, increases in variance should lead to greater censoring for the groups whose true scores fall at either end of the distribution. The current study used simulation methods to examine the influence of single-item Likert-type scale usage on ICC(1), ICC(2), and group-level correlations. Results revealed substantial underestimation of ICC(1) when using Likert-type scales with common response formats (e.g., 5 points). ICC(2) and group-level correlations were also underestimated, but to a lesser extent. Finally, the magnitude of underestimation was driven in large part to an interaction between Likert-type scale usage and the amounts of within- and between-group variance.
Comparison of Methods of Handling Missing Time-Invariant Covariates in Latent Growth Models Under the Assumption of Missing Completely at Random
Authors: Cheung Mike W.-L.
Published: July 2007

Latent growth models implemented in multilevel models (MLM) or structural equation models (SEM) may be used to analyze longitudinal data with an emphasis on interindividual and intraindividual differences. The main objective of this study is to compare methods of handling missing time-invariant data under the assumption of missing completely at random. Listwise deletion (LD), mean substitution (MS), the expectation-maximization (EM) algorithm, multiple imputation (MI), and full information maximum likelihood (FIML) are compared via a computer simulation study. The findings show that FIML and LD generally perform best, whereas the standard errors of EM and MI are usually underestimated. The results on MS are generally acceptable except when the percentage of missingness is large. Practical implications and directions for future research are discussed.
Bayesian Variance Estimation for Meta-Analysis
Authors: Steel Piers D. G. , Kammeyer-Mueller John
Published: July 2007

A primary goal in meta-analysis is determining the variance across a set of correlations after taking into account statistical and psychometric artifacts. If the residual variance is large, substantive moderators of the relationship likely exist; if there is little residual variance, the meta-analytic estimate of the effect size is expected to generalize across multiple settings. Surprisingly little attention has been directed toward some critical shortcomings of traditional methods for estimating residual variance. In this article, the authors argue that residual variance estimates are often based on an unrealistic model of the sampling distribution of residual variance. The authors review alternative Bayesian techniques for estimation that avoid these problems and provide simulation results demonstrating the superiority of the Bayesian approach.
The Relative Validity of Inferences About Mediation as a Function of Research Design Characteristics
Authors: Stone-Romero Eugene F. , Rosopa Patrick J.
Published: July 2007

Tests of assumed mediation models are common in the organizational sciences. However, the validity of inferences about mediation is a function of experimental design and the setting of a study. Regrettably, most tests of mediation have relied on the application of so-called ``causal modeling'' techniques to data from nonexperimental studies. As we demonstrate, inferences about the validity of assumed mediation models are highly suspect when they are based on the findings of nonexperimental research. One of the many reasons for this is the failure of the model being tested to be consistent with reality. Valid research-based inferences about mediation are possible. However, inferences from such tests are most likely to be valid when they are based on research that uses randomized experimental designs. Strategies for conducting research using these and other designs are described. Finally, we offer a set of conclusions and recommendations that stem from our analysis.
Testing Mediation and Suppression Effects of Latent Variables
Authors: Cheung Gordon W. , Lau Rebecca S.
Published: July 2007

Because of the importance of mediation studies, researchers have been continuously searching for the best statistical test for mediation effect. The approaches that have been most commonly employed include those that use zero-order and partial correlation, hierarchical regression models, and structural equation modeling (SEM). This study extends MacKinnon and colleagues (MacKinnon, Lockwood, Hoffmann, West, & Sheets, 2002; MacKinnon, Lockwood, & Williams, 2004, MacKinnon, Warsi, & Dwyer, 1995) works by conducting a simulation that examines the distribution of mediation and suppression effects of latent variables with SEM, and the properties of confidence intervals developed from eight different methods. Results show that SEM provides unbiased estimates of mediation and suppression effects, and that the bias-corrected bootstrap confidence intervals perform best in testing for mediation and suppression effects. Steps to implement the recommended procedures with Amos are presented.
Estimating Statistical Power With Incomplete Data
Authors: Davey Adam , Savla Jyoti
Published: July 2007

Software developments increasingly facilitate inclusion of incomplete data, but relatively little research has examined the effects of incomplete data on statistical power. Seven steps needed to conduct power analyses with incomplete data for a variety of commonly tested hypotheses are illustrated, focusing on significance tests of individual parameters. The example extends a growth curve model simulation presented by Curran and Muthén (1999) to the incomplete data situation. How to estimate statistical power for a range of sample sizes from a single model, as well as how to calculate the sample size required to obtain a desired value of statistical power, is demonstrated. Effects of data being missing completely at random (MCAR) or missing at random (MAR) across a range from 0% (complete data) to 95% missing data are considered. SAS and LISREL syntax are provided in this paper with syntax for other software available from the authors.
Multilevel Methods
Authors: Bliese Paul D. , Chan David , Ployhart Robert E.
Published: July 2007

The study of multilevel phenomena in organizations involves a complex interplay between methods and statistics on one hand and theory development on the other. In this introduction, the authors provide a short summary of the five articles in this feature topic and use them as a platform to discuss the broad need for work in the two areas of (a) multilevel construct validation and measurement and (b) statistical advances in variance decomposition. Within these two broad frameworks, the authors specifically discuss, first, the need to continue moving beyond notions of isomorphism in developing and testing aggregate-level constructs. Second, they discuss the potential value of using discontinuous growth models to understand transitions in longitudinal studies. Finally, they discuss some of the issues surrounding the ability to decompose variance in multilevel modeling of dichotomous and other nonnormal outcome data.
The Multifaceted Nature of Measurement Artifacts and Its Implications for Estimating Construct-Level Relationships
Authors: Le Huy , Schmidt Frank L. , Putka Dan J.
Published: July 2007

Measurement artifacts, including measurement errors and scale-specific factors, distort observed correlations between measures of psychological and organizational constructs. The authors discuss two alternative procedures, one using the generalized coefficient of equivalence and stability (GCES) and one based on structural equation modeling, to correct for the biasing effect of measurement artifacts in order to estimate construct-level relationships. Assumptions underlying the procedures are discussed and the degrees of biases resulting from violating the assumptions are examined by means of Monte Carlo simulation. They then propose an approach using cumulative knowledge in the literature about properties of measures of a construct to estimate the GCES. That approach can allow researchers to estimate relationships between constructs in most research situations. The authors apply the approach to estimate the GCES for overall job satisfaction, an important organizational construct.
Meta-Analysis
Authors: Schmidt Frank
Published: July 2007

During the past 30 years, meta-analysis has been an indispensable tool for revealing the hidden meaning of our research literatures. The four articles in this special section on meta-analysis illustrate some of the complexities entailed in meta-analysis methods. Although meta-analysis is a powerful tool for advancing cumulative knowledge, researchers can be confused by the complicated issues involved in the methodology. Each of these four articles contributes both to advancing this methodology and to the increasing complexities that can befuddle researchers. In these comments, the author attempts to clarify both of these aspects and provide a perspective on the methodological issues examined in these articles.
Incidence of Salmonellosis in Local Hens' Eggs
Authors: Camilleri Franklin
Published: July 2007

Evidence indicates that outbreaks of salmonellosis may be due to infected eggs. This prompted a study on the incidence of salmonella in eggs. This study was done during summer 1991 and 900 eggs were examined in all. None of the eggs examined were found to be infected with salmonella. However, the result obtained should be treated with care and analysed with a critical eye. The result obtained does not imply that local flocks are not infected by salmonella.
Environmental Health and The South African Community
Authors: Kocks D.J. , Corder C.K.
Published: July 2007

The success of an environmental impact assessment programme will depend on the perceptions of a community. There are differences in the opinion of the population groups of South Africa concerning the perceived environmental threats to health
Modeling the Principles of Community-Based Participatory Research in a Community Health Assessment Conducted by a Health Foundation
Authors: Williams Karen Jaynes , Gail Bray Patricia , Shapiro-Mendoza Carrie K. , Reisz Ilana , Peranteau Jane
Published: July 2007

The authors discuss strategies used and lessons learned by a health foundation during development of a community health assessment model incorporating community-based participatory research (CBPR) approaches. The assessment model comprises three models incorporating increasing amounts of CPBR principles. Model A combines local-area analysis of quantitative data, qualitative information (key informants, focus groups), and asset mapping. Model B, a community-based participatory model, emphasizes participatory rural appraisal approaches and quantitative assessment using rapid epidemiological assessment. Model C, a modified version of Model B, is financially more sustainable for our needs than Model B. The authors (a) describe origins of these models and illustrate practical applications and (b) explore the lessons learned in their transition from a traditional, nonparticipatory, quantitative approach to participatory approaches to community-health assessment. It is hoped that this article will contribute to the growing body of knowledge of practical aspects of incorporating CBPR approaches into community health assessments.
Nurse Staffing and Adverse Events in Hospitalized Children
Authors: Mark Barbara A. , Harless David W. , Berman Wallace F.
Published: July 2007

This study determined whether the number of hours of care provided by RNs was related to mortality and complications in hospitalized children. Administrative data (1996-2001) were used to examine discharges of 3.65 million pediatric patients in 286 general and children's hospitals in California. A greater number of resource-adjusted hours of care provided by RNs was related to significantly reduced occurrences of postoperative pulmonary complications, postoperative pneumonia, and postoperative septicemia; the positive impact of increases in nurse staffing was of greater magnitude at institutions providing fewer resource-adjusted hours of RN care. There was also evidence of an impact of increases in nurse staffing on urinary tract infections, but it was statistically significant only for institutions with higher resource-adjusted hours of RN care. There was no statistically significant relationship between RN staffing and mortality. More hours of care provided by RNs was associated with improved quality of care for hospitalized pediatric patients.
Effects of the deletion of the Escherichia coli frataxin homologue CyaY on the respiratory NADH:ubiquinone oxidoreductase
Authors: Pohl Thomas , Walter Julia , Stolpe Stefan , Soufo Joel H Defeu , Grauman Peter L , Friedrich Thorsten
Published: July 2007

Background

Frataxin is discussed as involved in the biogenesis of iron-sulfur clusters. Recently it was discovered that a frataxin homologue is a structural component of the respiratory NADH:ubiquinone oxidoreductase (complex I) in Thermus thermophilus. It was not clear whether frataxin is in general a component of complex I from bacteria. The Escherichia coli homologue of frataxin is coined CyaY.

Results

We report that complex I is completely assembled to a stable and active enzyme complex equipped with all known iron-sulfur clusters in a cyaY mutant of E. coli. However, the amount of complex I is reduced by one third compared to the parental strain. Western blot analysis and live cell imaging of CyaY engineered with a GFP demonstrated that CyaY is located in the cytoplasm and not attached to the membrane as to be expected if it were a component of complex I.

Conclusion

CyaY plays a non-essential role in the assembly of complex I in E. coli. It is not a structural component but may transiently interact with the complex.
Analysis and prediction of antibacterial peptides
Authors: Lata Sneh , Sharma BK , Raghava GPS
Published: July 2007

Background

Antibacterial peptides are important components of the innate immune system, used by the host to protect itself from different types of pathogenic bacteria. Over the last few decades, the search for new drugs and drug targets has prompted an interest in these antibacterial peptides. We analyzed 486 antibacterial peptides, obtained from antimicrobial peptide database APD, in order to understand the preference of amino acid residues at specific positions in these peptides.

Results

It was observed that certain types of residues are preferred over others in antibacterial peptides, particularly at the N and C terminus. These observations encouraged us to develop a method for predicting antibacterial peptides in proteins from their amino acid sequence. First, the N-terminal residues were used for predicting antibacterial peptides using Artificial Neural Network (ANN), Quantitative Matrices (QM) and Support Vector Machine (SVM), which resulted in an accuracy of 83.63%, 84.78% and 87.85%, respectively. Then, the C-terminal residues were used for developing prediction methods, which resulted in an accuracy of 77.34%, 82.03% and 85.16% using ANN, QM and SVM, respectively. Finally, ANN, QM and SVM models were developed using N and C terminal residues, which achieved an accuracy of 88.17%, 90.37% and 92.11%, respectively. All the models developed in this study were evaluated using five-fold cross validation technique. These models were also tested on an independent or blind dataset.

Conclusion

Among antibacterial peptides, there is preference for certain residues at N and C termini, which helps to demarcate them from non-antibacterial peptides. Both the termini play a crucial role in imparting the antibacterial property to these peptides. Among the methods developed, SVM shows the best performance in predicting antibacterial peptides followed by QM and ANN, in that order. AntiBP (Antibacterial peptides) will help in discovering efficacious antibacterial peptides, which we hope will prove to be a boon to combat the dreadful antibiotic resistant bacteria. A user friendly web server has also been developed to help the biological community, which is accessible at http://www.imtech.res.in/raghava/antibp/.
Proteomic screen in the simple metazoan Hydra identifies 14-3-3 binding proteins implicated in cellular metabolism, cytoskeletal organisation and Ca2+ signalling
Authors: Pauly Barbara , Lasi Margherita , MacKintosh Carol , Morrice Nick , Imhof Axel , Regula Jörg , Rudd Stephen , David Charles N , Böttger Angelika
Published: July 2007

Background

14-3-3 proteins have been implicated in many signalling mechanisms due to their interaction with Ser/Thr phosphorylated target proteins. They are evolutionarily well conserved in eukaryotic organisms from single celled protozoans and unicellular algae to plants and humans. A diverse array of target proteins has been found in higher plants and in human cell lines including proteins involved in cellular metabolism, apoptosis, cytoskeletal organisation, secretion and Ca2+signalling.

Results

We found that the simple metazoanHydrahas four 14-3-3 isoforms. In order to investigate whether the diversity of 14-3-3 target proteins is also conserved over the whole animal kingdom we isolated 14-3-3 binding proteins fromHydra vulgarisusing a 14-3-3-affinity column. We identified 23 proteins that covered most of the above-mentioned groups. We also isolated several novel 14-3-3 binding proteins and theHydraspecific secreted fascin-domain-containing protein PPOD. In addition, we demonstrated that one of the 14-3-3 isoforms, 14-3-3 HyA, interacts with oneHydra-Bcl-2 like protein in vitro.

Conclusion

Our results indicate that 14-3-3 proteins have been ubiquitous signalling components since the start of metazoan evolution. We also discuss the possibility that they are involved in the regulation of cell numbers in response to food supply inHydra.
Use of tiling array data and RNA secondary structure predictions to identify noncoding RNA genes
Authors: Weile Christian , Gardner Paul P , Hedegaard Mads M , Vinther Jeppe
Published: July 2007

Background

Within the last decade a large number of noncoding RNA genes have been identified, but this may only be the tip of the iceberg. Using comparative genomics a large number of sequences that have signals concordant with conserved RNA secondary structures have been discovered in the human genome. Moreover, genome wide transcription profiling with tiling arrays indicate that the majority of the genome is transcribed.

Results

We have combined tiling array data with genome wide structural RNA predictions to search for novel noncoding and structural RNA genes that are expressed in the human neuroblastoma cell line SK-N-AS. Using this strategy, we identify thousands of human candidate RNA genes. To further verify the expression of these genes, we focused on candidate genes that had a stable hairpin structures or a high level of covariance. Using northern blotting, we verify the expression of 2 out of 3 of the hairpin structures and 3 out of 9 high covariance structures in SK-N-AS cells.

Conclusion

Our results demonstrate that many human noncoding, structured and conserved RNA genes remain to be discovered and that tissue specific tiling array data can be used in combination with computational predictions of sequences encoding structural RNAs to improve the search for such genes.
Complete sequence and organization of Antheraea pernyi nucleopolyhedrovirus, a dr-rich baculovirus
Authors: Nie Zuo-Ming , Zhang Zhi-Fang , Wang Dan , He Ping-An , Jiang Cai-Ying , Song Li , Chen Fang , Xu Jie , Yang Ling , Yu Lin-Lin , Chen Jian , Lv Zheng-Bing , Lu Jing-Jing , Wu Xiang-Fu , Zhang Yao-Zhou
Published: July 2007

Background

The completion and reporting of baculovirus genomes is extremely important as it advances our understanding of gene function and evolution. Due to the large number of viral genomes now sequenced it is very important that authors present significantly detailed analyses to advance the understanding of the viral genomes. However, there is no report of the Antheraea pernyi nucleopolyhedrovirus (AnpeNPV) genome.

Results

The genome of AnpeNPV, which infects Chinese tussah silkworm (Antheraea pernyi), was sequenced and analyzed. The genome was 126,629 bp in size. The G+C content of the genome, 53.4%, was higher than that of most of the sequenced baculoviruses. 147 open reading frames (ORFs) that putatively encode proteins of 50 or more amino acid residues with minimal overlap were determined. Of the 147 ORFs, 143 appeared to be homologous to other baculovirus genes, and 4 were unique to AnpeNPV. Furthermore, there are still 29 and 33 conserved genes present in all baculoviruses and all lepidopteran baculoviruses respectively. In addition, the total number of genes common to all lepidopteran NPVs is sill 74, however the 74 genes are somewhat different from the 74 genes identified before because of some new sequenced NPVs. Only 6 genes were found exclusively in all lepidopteran NPVs and 12 genes were found exclusively in all Group I NPVs. AnpeNPV encodes v-trex(Anpe115, a 3' to 5' repair exonuclease), which was observed only in CfMNPV and CfDEFNPV in Group I NPVs. This gene potentially originated by horizontal gene transfer from an ancestral host. In addition, AnpeNPV encodes two conotoxin-like gene homologues (ctls), ctl1 and ctl2, which were observed only in HycuNPV, OpMNPV and LdMNPV. Unlike other baculoviruses, only 3 typical homologous regions (hr s) were identified containing 2~9 repeats of a 30 bp-long palindromic core. However, 24 perfect or imperfect direct repeats (dr s) with a high degree of AT content were found within the intergenic spacer regions that may function as non-hr, ori-like regions found in GrleGV, CpGV and AdorGV. 9 dr s were also found in intragenic spacer regions of AnpeNPV.

Conclusion

AnpeNPV belongs to Group I NPVs and is most similar to HycuNPV, EppoNPV, OpMNPV and CfMNPV based on gene content, genome arrangement, and amino acid identity. In addition, analysis of genes that flank hr s supported the argument that these regions are involved in the transfer of sequences between the virus and host.
Identification of unannotated exons of low abundance transcripts in Drosophila melanogaster and cloning of a new serine protease gene upregulated upon injury
Authors: Maia Rafaela M , Valente Valeria , Cunha Marco AV , Sousa Josane F , Araujo Daniela D , Silva Wilson A , Zago Marco A , Dias-Neto Emmanuel , Souza Sandro J , Simpson Andrew JG , Monesi Nadia , Ramos Ricardo GP , Espreafico Enilza M , Paçó-Larson Maria L
Published: July 2007

Background

The sequencing of the D.melanogaster genome revealed an unexpected small number of genes (~ 14,000) indicating that mechanisms acting on generation of transcript diversity must have played a major role in the evolution of complex metazoans. Among the most extensively used mechanisms that accounts for this diversity is alternative splicing. It is estimated that over 40% of Drosophila protein-coding genes contain one or more alternative exons. A recent transcription map of the Drosophila embryogenesis indicates that 30% of the transcribed regions are unannotated, and that 1/3 of this is estimated as missed or alternative exons of previously characterized protein-coding genes. Therefore, the identification of the variety of expressed transcripts depends on experimental data for its final validation and is continuously being performed using different approaches. We applied the Open Reading Frame Expressed Sequence Tags (ORESTES) methodology, which is capable of generating cDNA data from the central portion of rare transcripts, in order to investigate the presence of hitherto unnanotated regions of Drosophila transcriptome.

Results

Bioinformatic analysis of 1,303 Drosophila ORESTES clusters identified 68 sequences derived from unannotated regions in the current Drosophila genome version (4.3). Of these, a set of 38 was analysed by polyA+ northern blot hybridization, validating 17 (50%) new exons of low abundance transcripts. For one of these ESTs, we obtained the cDNA encompassing the complete coding sequence of a new serine protease, named SP212. The SP212 gene is part of a serine protease gene cluster located in the chromosome region 88A12-B1. This cluster includes the predicted genes CG9631, CG9649 and CG31326, which were previously identified as up-regulated after immune challenges in genomic-scale microarray analysis. In agreement with the proposal that this locus is co-regulated in response to microorganisms infection, we show here that SP212 is also up-regulated upon injury.

Conclusion

Using the ORESTES methodology we identified 17 novel exons from low abundance Drosophila transcripts, and through a PCR approach the complete CDS of one of these transcripts was defined. Our results show that the computational identification and manual inspection are not sufficient to annotate a genome in the absence of experimentally derived data.
The functional modulation of epigenetic regulators by alternative splicing
Authors: Lois Sergio , Blanco Noemí , Martínez-Balbás Marian , de la Cruz Xavier
Published: July 2007

Background

Epigenetic regulators (histone acetyltransferases, methyltransferases, chromatin-remodelling enzymes, etc) play a fundamental role in the control of gene expression by modifying the local state of chromatin. However, due to their recent discovery, little is yet known about their own regulation. This paper addresses this point, focusing on alternative splicing regulation, a mechanism already known to play an important role in other protein families, e.g. transcription factors, membrane receptors, etc.

Results

To this end, we compiled the data available on the presence/absence of alternative splicing for a set of 160 different epigenetic regulators, taking advantage of the relatively large amount of unexplored data on alternative splicing available in public databases. We found that 49 % (70 % in human) of these genes express more than one transcript. We then studied their alternative splicing patterns, focusing on those changes affecting the enzyme's domain composition. In general, we found that these sequence changes correspond to different mechanisms, either repressing the enzyme's function (e.g. by creating dominant-negative inhibitors of the functional isoform) or creating isoforms with new functions.

Conclusion

We conclude that alternative splicing of epigenetic regulators can be an important tool for the function modulation of these enzymes. Considering that the latter control the transcriptional state of large sets of genes, we propose that epigenetic regulation of gene expression is itself strongly regulated by alternative splicing.
Roles of curli, cellulose and BapA in Salmonella biofilm morphology studied by atomic force microscopy
Authors: Jonas Kristina , Tomenius Henrik , Kader Abdul , Normark Staffan , Römling Ute , Belova Lyubov M , Melefors Öjar
Published: July 2007

Background

Curli, cellulose and the cell surface protein BapA are matrix components in Salmonella biofilms. In this study we have investigated the roles of these components for the morphology of bacteria grown as colonies on agar plates and within a biofilm on submerged mica surfaces by applying atomic force microscopy (AFM) and light microscopy.

Results

AFM imaging was performed on colonies of Salmonella Typhimurium grown on agar plates for 24 h and on biofilms grown for 4, 8, 16 or 24 h on mica slides submerged in standing cultures. Our data show that in the wild type curli were visible as extracellular material on and between the cells and as fimbrial structures at the edges of biofilms grown for 16 h and 24 h. In contrast to the wild type, which formed a three-dimensional biofilm within 24 h, a curli mutant and a strain mutated in the global regulator CsgD were severely impaired in biofilm formation. A mutant in cellulose production retained some capability to form cell aggregates, but not a confluent biofilm. Extracellular matrix was observed in this mutant to almost the same extent as in the wild type. Overexpression of CsgD led to a much thicker and a more rapidly growing biofilm. Disruption of BapA altered neither colony and biofilm morphology nor the ability to form a biofilm within 24 h on the submerged surfaces. Besides curli, the expression of flagella and pili as well as changes in cell shape and cell size could be monitored in the growing biofilms.

Conclusion

Our work demonstrates that atomic force microscopy can efficiently be used as a tool to monitor the morphology of bacteria grown as colonies on agar plates or within biofilms formed in a liquid at high resolution.
Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice
Authors: Kukar Thomas , Prescott Sonya , Eriksen Jason L , Holloway Vallie , Murphy M Paul , Koo Edward H , Golde Todd E , Nicolle Michelle M
Published: July 2007

Background

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Aβ42 in cell culture and animal models, and that the effect of NSAIDs on Aβ42 is independent of the inhibition of cyclooxygenase by these compounds. Since Aβ42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Aβ42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Aβ42 lowering agent with greatly reduced cyclooxygenase activity that shows promise for testing this hypothesis. In this study we report the effect of chronic R-flurbiprofen treatment on cognition and Aβ loads in Tg2576 APP mice.

Results

A four-month preventative treatment regimen with R-flurbiprofen (10 mg/kg/day) was administered to young Tg2576 mice prior to robust plaque or Aβ pathology. This treatment regimen improved spatial learning as assessed by the Morris water maze, indicated by an increased spatial bias during the third probe trial and an increased utilization of a place strategy to solve the water maze. These results are consistent with an improvement in hippocampal- and medial temporal lobe-dependent memory function. A modest, though not statistically significant, reduction in formic acid-soluble levels of Aβ was also observed. To determine if R-flurbiprofen could reverse cognitive deficits in Tg2576 mice where plaque pathology was already robust, a two-week therapeutic treatment was given to older Tg2576 mice with the same dose of R-flurbiprofen. This approach resulted in a significant decrease in Aβ plaque burden but no significant improvement in spatial learning.

Conclusion

We have found that chronic administration of R-flurbiprofen is able to attenuate spatial learning deficits if given prior to plaque deposition in Tg2576 mice. Given its ability to selectively target Aβ42 production and improve cognitive impairments in transgenic APP mice, as well as promising data from a phase 2 human clinical trial, future studies are needed to investigate the utility of R-flurbiprofen as an AD therapeutic and its possible mechanisms of action.
Endoscopists attitudes on the publication of "quality" data for endoscopic procedures: a cross-sectional survey
Authors: Hearnshaw Sarah A , Maddock Helena M , Nylander David , Prince Martin I
Published: July 2007

Background

Whilst the public now have access to mortality & morbidity data for cardiothoracic surgeons, such "quality" data for endoscopy are not generally available. We studied endoscopists' attitudes to and the practicality of this data being published.

Methods

We sent a questionnaire to all consultant gastrointestinal (GI) surgeons, physicians and medical GI specialist registrars in the Northern region who currently perform GI endoscopic procedures (n = 132). We recorded endoscopist demographics, experience and current data collection practice. We also assessed the acceptability and utility of nine items describing endoscopic "quality" (e.g. mortality, complication & completion rates).

Results

103 (78%) doctors responded of whom 79 were consultants (77%). 61 (59%) respondents were physicians. 77 (75%) collect any "quality" data. The most frequently collected item was colonoscopic completion rate. Data were most commonly collected for appraisal, audit or clinical governance. The majority of doctors (54%) kept these data only available to themselves, and just one allowed the public to access this. The most acceptable data item was annual number of endoscopies and the least was crude upper GI bleeding mortality. Surgeons rated information less acceptable and less useful than physicians. Acceptability and utility scores were not related to gender, length of experience or current activity levels. Only two respondents thought all items totally unacceptable and useless.

Conclusion

The majority of endoscopists currently collect "quality" data for their practice although these are not widely available. The endoscopists in this study consider the publication of their outcome data to be "fairly unacceptable/not very useful" to "neutral" (score 2–3). If these data were made available to patients, consideration must be given to both its value and its acceptability.
Resequencing PNMTin European hypertensive and normotensive individuals: no common susceptibilily variants for hypertension and purifying selection on intron 1
Authors: Kepp Katrin , Juhanson Peeter , Kozich Viktor , Ots Mai , Viigimaa Margus , Laan Maris
Published: July 2007

Background

Human linkage and animal QTL studies have indicated the contribution of genes on Chr17 into blood pressure regulation. One candidate gene is PNMT, coding for phenylethanolamine-N-methyltransferase, catalyzing the synthesis of epinephrine from norepinephrine.

Methods

Fine-scale variation of PNMT was screened by resequencing hypertensive (n = 50) and normotensive (n = 50) individuals from two European populations (Estonians and Czechs). The resulting polymorphism data were analyzed by statistical genetics methods using Genepop 3.4, PHASE 2.1 and DnaSP 4.0 software programs. In silico prediction of transcription factor binding sites for intron 1 was performed with MatInspector 2.2 software.

Results

PNMT was characterized by minimum variation and excess of rare SNPs in both normo- and hypertensive individuals. None of the SNPs showed significant differences in allelic frequencies among population samples, as well as between screened hypertensives and normotensives. In the joint case-control analysis of the Estonian and the Czech samples, hypertension patients had a significant excess of heterozygotes for two promoter region polymorphisms (SNP-184; SNP-390). The identified variation pattern of PNMT reflects the effect of purifying selection consistent with an important role of PNMT-synthesized epinephrine in the regulation of cardiovascular and metabolic functions, and as a CNS neurotransmitter. A striking feature is the lack of intronic variation. In silico analysis of PNMT intron 1 confirmed the presence of a human-specific putative Glucocorticoid Responsive Element (GRE), inserted by Alu-mediated transfer. Further analysis of intron 1 supported the possible existence of a full Glucocorticoid Responsive Unit (GRU) predicted to consist of multiple gene regulatory elements known to cooperate with GRE in driving transcription. The role of these elements in regulating PNMT expression patterns and thus determining the dynamics of the synthesis of epinephrine is still to be studied.

Conclusion

We suggest that the differences in PNMT expression between normotensives and hypertensives are not determined by the polymorphisms in this gene, but rather by the interplay of gene expression regulators, which may vary among individuals. Understanding the determinants of PNMT expression may assist in developing PNMT inhibitors as potential novel therapeutics.