bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prevalence of Stalking Among Finnish University Students
Authors: Björklund Katja , Häkkänen-Nyholm Helinä , Sheridan Lorraine , Roberts Karl
Published: January 2010

The present study examined the prevalence and nature of stalking among university students in Finland. The prevalence of stalking was analyzed in relation to stalking episodes, violent stalking victimization, the stalker—victim relationship, and stalking duration. A group of Finnish university students were contacted by e-mail and asked to participate in a stalking survey. In total, 615 students participated. Almost one fourth of the respondents (22.3%) had experienced one episode (i.e., period of time) of stalking, and more than one fourth (26.2%) reported being stalked two or more episodes (i.e., periods of time) in their lifetime. More than half (55%) of the stalkers were acquaintances, 25% were ex-partners, and 19% were strangers. The mean duration of stalking was 10 months. Stalking duration was significantly associated with stalker gender and prior victim—stalker relationship. Almost half of those being stalked (46%) had been exposed to violent or threatening behavior. Ex-partner stalkers were most likely to use violence as well as a wide range of violent stalking methods. Logistic regression analysis revealed significant independent associations between stalking violence and stalking behaviors. Stalking is highly prevalent among Finnish university students; it is maintained, on average, for a relatively long period; and it often includes some form of violence and/or threats. The results suggest that health care professionals require screening methods and schooling concerning stalking.
An Analysis of Race and Ethnic Categories in Career Research From 1990 to 2007
Authors: Wells Eliza M. , Delgado-Romero Edward A. , Shelton Kimber L.
Published: January 2010

Previous research concerning the reporting of race and ethnicity in empirical research was replicated and expanded. One thousand two hundred sixty-eight studies over the years 1990—2007 were examined in the following journals: Career Development Quarterly, Journal of Career Assessment, Journal of Career Development, and Journal of Vocational Behavior. Results indicated that 62% of studies from 1990 to 1999 and 46% from 2000 to 2007 do not report race or ethnicity at all. A racial/ethnic profile of the research participants over the 18-year period was constructed and compared with the U.S. population for that time period, as well as to previous research. The authors provide implications and suggestions for future research.
Perceptions of Women in Management: A Thematic Analysis of Razing the Glass Ceiling
Authors: Baumgartner Mindy S. , Schneider David E.
Published: January 2010

Despite advances that women have made in organizations over the past century, women continue to be underrepresented in upper management positions. Based on a review of literature, six issues that women face when encountering the glass ceiling were examined. The goal of the current study involved having women who have succeeded at breaking the glass ceiling in their own careers speak to these issues. Thematic analysis was used on data from qualitative interviews with seven women in different fields who have broken the glass ceiling at varying levels in their organizations. Collectively, responses provide suggestions for overcoming stereotypes, contending with the Old Boys network, balancing work and family, choosing mentors, understanding the queen bee syndrome, developing a leadership style, and determining personal aspirations for advancement. Results may serve as advice for women who face the glass ceiling in their own careers. Directions for future research are offered.
Impact of lupus on school attendance and performance
Authors: Moorthy LN , Peterson MGE , Hassett A. , Baratelli M. , Lehman TJA
Published: January 2010

Cognitive impairment in children and adolescents with systemic lupus erythematosus (SLE) can affect intelligence, academic achievement, arithmetic, reading comprehension, learning, visual memory and complex problem solving ability. In this prospective two-center study, we examined children’s (and adolescents’) and parents’ perception of the impact of SLE on school; the relationship between child and parent reports on school-related issues; and the relationship between health-related quality of life (HRQOL) and school-related issues. Patients aged 9—18 years with SLE and their parents completed corresponding child and parent reports of the SLE-specific HRQOL scale, Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY©), and PedsQLTM generic and rheumatology modules. Patients also completed questions related to school attendance and performance. Qualified physicians assessed SLE activity, damage and severity. Forty-one patients (73% girls) with SLE with mean age of 15 ± 3 years and 32 parents participated. Mean school domain scores for child and parent reports of the PedsQL TM generic report were lower compared with total and subscale scores. Patients reported difficulty with schoolwork, had problems with memory and concentration, and were sad about the effect of SLE on schoolwork and attendance. Moderate to strong correlations were found between child and parent reports on school-related items from all questionnaires. Eighty-three percent of patients felt that they would have done better in school if they did not have SLE. Moderate correlations (r = 0.3—0.4) were found between SMILEY © total score and the following items: satisfaction with school performance, interest in schoolwork, remembering what was learned, and concentrating in class. Patients on intravenous chemotherapeutic medications missed more school days (p < 0.05) compared with patients on oral medications. Also, patients with a greater number of missed school days had increased disease activity (p = 0.008). SLE and activities related to caring for the disease clearly impose a burden on children’s school attendance and performance. School-related activities can have a significant impact on HRQOL in children and adolescents with SLE. Detailed examination of the impact of SLE on attendance and the various aspects of school performance will enable us to formulate interventions in school for these children and adolescents. Lupus (2010) 19, 620—627.
Effect of chloroquine phosphate treatment on serum MMP-9 and TIMP-1 levels in patients with systemic lupus erythematosus
Authors: Lesiak A. , Narbutt J. , Sysa-Jedrzejowska A. , Lukamowicz J. , McCauliffe DP , Wózniacka A.
Published: January 2010

Antimalarials are widely used for the treatment of systemic lupus erythematosus. However, their mechanisms of action have not been fully elucidated. Literature data indicate that matrix metalloproteinases may play a role in the immune response and tissue damage that occur in autoimmune skin diseases. The aim of this study was to determine the effect of 3 months of chloroquine treatment on serum levels of MMP-9 and TIMP-1 in patients with systemic lupus erythematosus. The study group consisted of 25 patients with systemic lupus erythematosus and 25 sex- and age-matched healthy volunteers. Before drug administration, serum levels of MMP-9 and TIMP-1 were determined by enzyme-linked immunosorbent assay. The same procedure was performed after chloroquine treatment. We found significantly higher median serum levels of MMP-9 in patients with systemic lupus erythematosus before therapy (57.20 ng/ml) when compared with controls (44.50 ng/ml) (p < 0.001). After chloroquine therapy the median MMP-9 serum level of systemic lupus erythematosus patients decreased significantly (43 ng/ml; p < 0.001). Before treatment the median TIMP-1 serum level in the patients with systemic lupus erythematosus was significantly higher than in the control group (500 vs. 200 ng/ml; p < 0.001), and after therapy it increased significantly (750 ng/ml TIMP-1; p < 0.001). The results suggest that chloroquine treatment may affect the matrix metalloproteinase network, and this effect may contribute to the immunoregulatory and anti-inflammatory properties of antimalarials.
Mucormycosis complications in systemic lupus erythematosus
Authors: Arce-Salinas CA , Pérez-Silva E.
Published: January 2010

This case involved a 75-year-old woman with systemic lupus erythematosus. Two months previously, she had a flare that was treated successfully by increasing the dosages of prednisone and azathioprine. A sudden onset of ocular pain, diplopia, and loss of vision suggestive of optical neuritis or vascular involvement confused the issue, and rhinocerebral zygomycosis was demonstrated later. We review the presentations of this fungal infection in patients with systemic lupus erythematosus with emphasis on its initial features.
Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis
Authors: Lee YH , Woo J-H. , Choi SJ , Ji JD , Song GG
Published: January 2010

The aim of this study was to assess the efficacies and toxicities of immunosuppressive treatments for lupus nephritis (LN) versus cyclophosphamide (CYC). A meta-analysis was performed to determine treatment efficacy and toxicity outcomes between mycophenolate mofetil (MMF) and CYC induction therapies, between MMF and azathioprine (AZA) as maintenance therapies, and between low-dose intravenous (IV) CYC and high-dose IV CYC therapy. Ten randomized controlled trials (RCTs) were included in the meta-analysis. In terms of induction therapies, MMF did not increase complete remission or partial remission rates as compared with CYC. However, the relative risks (RRs) of amenorrhea and leukopenia tended to be lower in the MMF group than in the CYC group. Meta-analysis of MMF versus AZA as a maintenance therapy showed no difference between the two groups in terms of response rates or the risk of developing end-stage renal disease. Low-dose IV CYC therapy had lower relapse rates than high-dose IV CYC therapy (RR 0.465, 95% confidence interval [CI] 0.261—0.830, p-value 0.010), and was associated with a lower infection risk (RR 0.688, 95% CI 0.523—0.905, p-value 0.008). In conclusion, MMF was found to be as effective as CYC and tended to have a better safety profile as an induction therapy for LN than CYC.
High-density lipoprotein inversely relates to its specific autoantibody favoring oxidation in thrombotic primary antiphospholipid syndrome
Authors: Ames PRJ , Matsuura E. , Batuca JR , Ciampa A. , Lopez LL , Ferrara F. , Iannaccone L. , Delgado Alves J.
Published: January 2010

Abnormalities of the lipid profile partly explain the atherogenic tendency of systemic lupus erythematosus but the picture is unclear in thrombotic primary antiphospholipid syndrome (PAPS). Herein we compare the lipid profile, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (CHO), apolipoprotein A (ApoA-I), apolipoprotein B (ApoB), tryglicerides (TRY)), anti-lipoprotein antibodies, beta-2-glycoprotein I complexed to oxidized low-density lipoprotein (oxLDL-ß2GPI) and C-reactive protein (CRP) from thrombotic PAPS (n = 34), thrombotic patients with inherited thrombophilia (IT; n = 36), subjects persistently positive for antiphospholipid antibodies (aPL, n = 18) with no underlying autoimmune or non-autoimmune disorders and healthy controls (n = 28) and determined the reciprocal effects of anti-lipoprotein antibodies, the lipid profile, oxLDL-ß2GPI and CRP. Average concentrations of HDL (p < 0.0001), LDL (p < 0.0001), CHO (p = 0.0002), ApoA-I (p = 0.002) were lower in PAPS whereas average TRY was higher (p = 0.01) than other groups. Moreover, the aPL and PAPS group showed higher levels of IgG anti-HDL (p = 0.01) and IgG anti-ApoA-I (p < 0.0001) whereas the PAPS group showed greater average oxLDL-ß2GPI (p = 0.001) and CRP (p = 0.003). Within the PAPS group, IgG anti-HDL correlated negatively to HDL (p = 0.004) and was an independent predictor of oxLDL-ß2GPI (p = 0.009). HDL and ApoA-I correlated negatively with CRP (p = 0.001 and p = 0.007, respectively). IgG anti-HDL may hamper the antioxidant and anti-inflammatory effect of HDL favoring low-grade inflammation and enhanced oxidation in thrombotic PAPS. Lupus (2010) 19, 711—716.
A Meta-Analysis of Motivational Interviewing: Twenty-Five Years of Empirical Studies
Authors: Lundahl Brad W. , Kunz Chelsea , Brownell Cynthia , Tollefson Derrik , Burke Brian L.
Published: January 2010

Objective: The authors investigated the unique contribution motivational interviewing (MI) has on counseling outcomes and how MI compares with other interventions. Method: A total of 119 studies were subjected to a meta-analysis. Targeted outcomes included substance use (tobacco, alcohol, drugs, marijuana), health-related behaviors (diet, exercise, safe sex), gambling, and engagement in treatment variables. Results: Judged against weak comparison groups, MI produced statistically significant, durable results in the small effect range (average g = 0.28). Judged against specific treatments, MI produced nonsignificant results (average g = 0.09). MI was robust across many moderators, although feedback (Motivational Enhancement Therapy [MET]), delivery time, manualization, delivery mode (group vs. individual), and ethnicity moderated outcomes. Conclusions: MI contributes to counseling efforts, and results are influenced by participant and delivery factors.
Unto Others: Illustrating the Human Capacity for Cooperation
Authors: Morris J. Andrew , Urbanski John , Hunt Jason
Published: January 2010

Research in both evolutionary economics and evolutionary psychology provides strong evidence that human behavior can be, and is, a complex mix of hedonism and altruism with a strong inclination toward cooperation under certain conditions. In this article, behavioral assumptions made in mainstream business theory are compared and contrasted with empirical findings generated from evolutionary theory. Drawing from an evolutionary foundation, the current article illustrates three widely available exercises that educators can use to (a) explore the human capacity for cooperation and others-directed behaviors and (b) counter the overreliance on self-interest to explain human behavior at work.
Tied Up and Isolated in the Schoolhouse
Authors: Mohr Wanda K. , LeBel Janice , O’Halloran Ronald , Preustch Christa
Published: January 2010

In 1999, the United States General Accountability Office (USGAO) investigated restraints and seclusion use in mental health settings and found patterns of misuse and abuse. A decade later, it found the same misuse and abuse in schools. Restraints and seclusion are traumatizing and dangerous procedures that have caused injury and death. In the past decade, restraints and seclusion have gone from being considered an essential part of the psychiatric mental health toolkit to being viewed as a symptom of treatment failure. In most mental health settings, the use of restraints and seclusion has plummeted due to federal regulations, staff education, and concerted effort of psychiatric national and local leadership. The purpose of this article is to provide a background to and an overview of the present imbroglio over restraints and seclusion in public and private schools, articulate their dangers, dispel myths and misinformation about them, and suggest a leadership role for school nurses in reducing the use of these procedures.
Compositional, Physical, Antioxidant and Sensory Characteristics of Novel Syrup from Date Palm (Phoenix dactylifera L.)
Authors: Ben Thabet I. , Besbes S. , Masmoudi M. , Attia H. , Deroanne C. , Blecker C.
Published: January 2010

This study is a contribution to valorise date palm sap (Phoenix dactylifera L.) by elaboration of high quality syrup. Sap was concentrated by evaporation and the obtained product was characterized by its physicochemical, rheological, thermal, sensory properties and by its antioxidant activity. Syrups from date palm sap have a good nutritional value marked by high amounts of sugars (58—75 g/100 g fresh matter basis), minerals (2.1—2.6 g/100 g fresh matter basis) and phenolics (147.61—224.55 mg of ferulic acid equivalents/kg fresh weight). Syrup also presents an antioxidant activity that appears related to total phenolic content. Rheological properties indicate that syrup preserves a Newtonian behavior from 10 °C to 55 °C well modeled by Arrhenius equation. Hedonic evaluation showed that consumers’ appreciation of date palm syrup was not significantly different to the most known sap syrup: maple syrup.
A Comparative Analysis of Health-Related Quality of Life and Family Impact Between Children With ADHD Treated in a General Pediatric Clinic and a Psychiatric Clinic Utilizing the PedsQL
Authors: Limbers Christine A. , Ripperger-Suhler Jane , Boutton Kelly , Ransom Daniel , Varni James W.
Published: January 2010

Objective: To evaluate health-related quality of life (HRQOL) from the perspective of children with ADHD and their parents being seen in a Pediatric Clinic in comparison to healthy children and children with ADHD being seen in a Psychiatric Clinic. Method: Participants were children with a physician diagnosis of ADHD ages 5-18 years and their parents ( n = 17, General Pediatric Clinic; n = 181, Psychiatric Clinic). Children and parents completed the PedsQL™ 4.0 Generic Core Scales. Parents completed the PedsQL Family Impact Module and Vanderbilt ADHD Diagnostic Rating Scales. Results: Pediatric patients with ADHD being seen in the Pediatric Clinic demonstrated substantially lower HRQOL in comparison to the matched healthy sample, and significantly higher HRQOL and family functioning than pediatric patients with ADHD being seen in the Psychiatric Clinic. Conclusion: These data demonstrate the substantial negative impact of ADHD on HRQOL from the perspective of both children and parents.)
A Pipelined Algorithm for Large, Irregular All-Gather Problems
Authors: Träff Jesper Larsson , Ripke Andreas , Siebert Christian , Balaji Pavan , Thakur Rajeev , Gropp William
Published: January 2010

We describe and evaluate a new pipelined algorithm for large, irregular all-gather problems. In the irregular allgather problem each process in a set of processes contributes individual data of possibly different size, and all processes have to collect all data from all processes. The pipelined algorithm is useful for the implementation of the MPI_Allgatherv collective operation of the Message-Passing Interface (MPI) for large problems. By conception, the new algorithm is well suited to implementation on clustered multiprocessors, such as symmetric multiprocessing (SMP) clusters. The new algorithm has been implemented within different MPI libraries. Benchmark results on NEC SX-8, Linux clusters with InfiniBand and Gigabit Ethernet, IBM Blue Gene/P, and SiCortex systems show huge performance gains in accordance with the expected behavior.
Exploiting Direct Access Shared Memory for MPI On Multi-Core Processors
Authors: Brightwell Ron
Published: January 2010

In 2008, the Catamount lightweight kernel was extended to support direct access shared memory between processes running on the same compute node. This extension, called SMARTMAP, allows each process read/write access to another process’ memory by extending the virtual address of each process. Simple virtual address bit manipulation can be used to access the same virtual address in a different process’ address space. In this paper we describe an implementation of the Message Passing Interface (MPI) that uses SMARTMAP for intra-node message passing. SMARTMAP has several advantages over POSIX shared memory techniques for implementing MPI. We present performance results comparing MPI using SMARTMAP to the existing MPI transport layer on a quad-core Cray XT platform.
Madre: the Memory-Aware Data Redistribution Engine
Authors: Siegel Stephen F. , Siegel Andrew R.
Published: January 2010

We report on the development of a new computational framework for efficiently carrying out parallel data redistribution in a limited memory environment. This new library, MADRE (Memory-Aware Data Redistribution Engine), is an open-source, C/MPI-based toolkit designed for quick and easy integration into application codes that have demanding data migration needs. At the same time, MADRE exposes a lower-level application programming interface that greatly facilitates the development and incorporation of new algorithms into the MADRE framework, thus serving as a potential organizing entity for continued research in this area. Finally, we develop, describe, and test in detail several new parallel redistribution algorithms that are incorporated into the MADRE distribution.
A cost-effectiveness analysis of the Chlamydia Monday - A community-based intervention to decrease the prevalence of chlamydia in Sweden
Authors: Deogan Charlotte L. , Hansson Bocangel Marta K. , Wamala Sarah P. , Månsdotter Anna M.
Published: January 2010

Aims: The study was undertaken to assess the cost-effectiveness of the Chlamydia Monday, 2007. This is a community-based intervention aimed at reducing the prevalence of chlamydia by information and increased availability of testing, treatment and contact tracing in Stockholm. The aim was to analyze the cost-effectiveness by estimating costs, savings and effects on health associated with the intervention, and to determine if cost-effectiveness varies between men and women. Methods: A societal perspective was adopted, meaning all significant costs and consequences were taken into consideration, regardless of who experienced them. A cost-effectiveness model was constructed including costs of the intervention, savings due to avoiding potential costs associated with medical sequels of chlamydia infection, and health gains measured as quality adjusted life years (QALY). Sensitivity analyses were done to explore model and result uncertainty. Results: Total costs were calculated to be 66,787.21; total savings to 30,370.14; and total health gains to 9.852324 QALYs (undiscounted figures). The discounted cost per QALY was 8,346.05 (10,810.77/QALY for women and 6,085.35/QALY for men). Sensitivity analyses included changes in effectiveness, variation of prevalence, reduced risk of sequel progression, inclusion of prevented future production loss and shortened duration for chronic conditions. The cost per QALY was consistently less than 50,000, which is often regarded as cost-effective in a Swedish context. Conclusions: The Chlamydia Monday has been demonstrated by this study to be a cost-effective intervention and should be considered a wise use of society’s resources.
Infection outbreaks in acute hospitals: a systems approach
Authors: Waterson Patrick
Published: January 2010

This paper puts forward the case for applying a systems approach to the analysis of hospital-based infection outbreaks. A major advantage of the systems approach is that it affords insights into how actions or occurrences at one system level (e.g. individual error) collectively interact with team (e.g. leadership style) and organisational (e.g. safety culture) levels of analysis. Most of the research concerned with behavioural aspects of infection control has focused on a single level of analysis (e.g. interventions to improve hand washing). The infection outbreaks at the Maidstone and Tunbridge Wells NHS Trust are used as a case study in order to demonstrate the usefulness of the systems approach. The paper further outlines the human and organisational issues raised by the analysis and provides a means through which these aspects of infection can be highlighted as part of a future research agenda.
Treatment of latent Mycobacterium tuberculosis infection in intravenous drug users co-infected with HIV
Authors: Sánchez Francesca , Balagué Montse , García de Olalla Patricia , López Colomés José L. , Martín Vicente , Guerrero Rafael , Marco Andrés , Caylà Joan A.
Published: January 2010

Objective: This clinical trial, carried out among injection drug users and the HIV-infected with tuberculin skin test ≥ 5 mm, aimed to evaluate the compliance and tolerability of two preventive strategies against tuberculosis (TB).

Methods: Study protocol prospectively compares adherence to nine months of daily therapy with isoniazid (9H) versus two months of daily therapy with rifampin plus pyrazinamide (2RZ) administered randomly. All patients were concurrently admitted to a methadone maintenance programme. To assess toxicity, liver function was monitored monthly.

Results: From 305 assessable patients, those in 2RZ arm showed better adherence (84% vs. 59%, p < 0.0001). Results on liver toxicity did not show significant differences between 9H and 2RZ (4.5% vs. 6.9%; odds ratio = 1.58, 95% confidence interval = 0.42—7.24). Conclusion: 2RZ should be considered an option to prevent TB in selected groups of patients infected with HIV, such as injection drug users on methadone treatment.
Deletion of the p110β isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo
Authors: Martin Valérie , Guillermet-Guibert Julie , Chicanne Gaétan , Cabou Cendrine , Jandrot-Perrus Martine , Plantavid Monique , Vanhaesebroeck Bart , Payrastre Bernard , Gratacap Marie-Pierre
Published: January 2010

During platelet activation, phosphoinositide 3-kinases (PI3Ks) produce lipid second messengers participating in the regulation of functional responses. Here, we generated a megakaryocyte-restricted p110β null mouse model and demonstrated a critical role of PI3Kβ in platelet activation via an immunoreceptor tyrosine-based activation motif, the glyco-protein VI-Fc receptor γ-chain complex, and its contribution in response to G-protein–coupled receptors. Interestingly, the production of phosphatidylinositol 3,4,5-trisphosphate and the activation of protein kinase B/Akt were strongly inhibited in p110β null platelets stimulated either via immunoreceptor tyrosine-based activation motif or G-protein–coupled receptors. Functional studies showed an important delay in fibrin clot retraction and an almost complete inability of these platelets to adhere onto fibrinogen under flow condition, suggesting that PI3Kβ is also acting downstream of αIIbβ3. In vivo studies showed that these mice have a normal bleeding time and are not protected from acute pulmonary thromboembolism but are resistant to thrombosis after FeCl3 injury of the carotid, suggesting that PI3Kβ is a potential target for antithrombotic drugs.
TAK1 targeting by glucocorticoids determines JNK and IκB regulation in Toll-like receptor–stimulated macrophages
Authors: Bhattacharyya Sandip , Ratajczak Christine K. , Vogt Sherri K. , Kelley Crystal , Colonna Marco , Schreiber Robert D. , Muglia Louis J.
Published: January 2010

Glucocorticoids potently attenuate the production of inflammatory mediators by macrophages, a primary effector of innate immunity. Activation of different macrophage Toll-like receptors (TLRs) by their respective ligands presents a powerful system by which to evaluate stimulus-dependent glucocorticoid effects in the same cell type. Here, we test the hypothesis that glucocorticoids, acting through the glucocorticoid receptor, modulate macrophage activation preferentially depending upon the TLR-selective ligand and TLR adapters. We established that 2 adapters, Trif, MyD88, or both, determine the ability of glucocorticoids to suppress inhibitor of κB (IκB) degradation or Janus kinase (JNK) activation. Moreover, the sensitivity of transforming growth factor β–activated kinase 1 (TAK1) activation to glucocorticoids determines these effects. These findings identify TAK1 as a novel target for glucocorticoids that integrates their anti-inflammatory action in innate immunity signaling pathways.
High BAALC expression predicts chemoresistance in adult B-precursor acute lymphoblastic leukemia
Authors: Kühnl Andrea , Gökbuget Nicola , Stroux Andrea , Burmeister Thomas , Neumann Martin , Heesch Sandra , Haferlach Torsten , Hoelzer Dieter , Hofmann Wolf-Karsten , Thiel Eckhard , Baldus Claudia D.
Published: January 2010

Overexpression of BAALC is an adverse prognostic factor in adults with cytogenetically normal acute myeloid leukemia and T-cell acute lymphoblastic leukemia (ALL). Here, we analyzed the prognostic significance of BAALC in B-precursor ALL. BAALC MRNA expression was determined in 368 primary adult B-precursor ALL patients enrolled on the 06/99 and 07/03 GMALL trials. Patients were grouped into tertiles according to BAALC expression (T1-T3). Higher BAALC expression (T3 vs T2 vs T1) was associated with higher age (P < .001), a higher white blood cell count (P = .008), CD34 (P = .001), BCR-ABL (P < .001), and MLL-AF4 (P < .001). Higher BAALC expression predicted primary therapy resistance in the overall cohort (P = .002) and in the BCR-ABL− and MLL-AF4− subgroup (P = .01). In BCR-ABL− and MLL-AF4− patients, higher BAALC expression was associated with a shorter overall survival (OS; 5-year OS: T3, 38%; T2, 52%; T1, 70%; P = .004) and independently predicted OS in multivariate models (P = .03). Gene-expression profiling revealed an up-regulation of stem cell markers and genes involved in chemoresistance (TSPAN7 and LYN) in the high BAALC group. Thus, high BAALC expression is associated with an immature, chemoresistant leukemic phenotype and identifies patients with inferior OS. Determination of BAALC might contribute to risk assessment of molecularly undefined adult B-precursor ALL.
FOG1 requires NuRD to promote hematopoiesis and maintain lineage fidelity within the megakaryocytic-erythroid compartment
Authors: Gregory Gregory D. , Miccio Annarita , Bersenev Alexey , Wang Yuhuan , Hong Wei , Zhang Zhe , Poncz Mortimer , Tong Wei , Blobel Gerd A.
Published: January 2010

Nuclear factors regulate the development of complex tissues by promoting the formation of one cell lineage over another. The cofactor FOG1 interacts with transcription factors GATA1 and GATA2 to control erythroid and megakaryocyte (MK) differentiation. In contrast, FOG1 antagonizes the ability of GATA factors to promote mast cell (MC) development. Normal FOG1 function in late-stage erythroid cells and MK requires interaction with the chromatin remodeling complex NuRD. Here, we report that mice in which the FOG1/NuRD interaction is disrupted (Fogki/ki) produce MK-erythroid progenitors that give rise to significantly fewer and less mature MK and erythroid colonies in vitro while retaining multilineage capacity, capable of generating MCs and other myeloid lineage cells. Gene expression profiling of Fogki/ki MK-erythroid progenitors revealed inappropriate expression of several MC-specific genes. Strikingly, aberrant MC gene expression persisted in mature Fogki/ki MK and erythroid progeny. Using a GATA1-dependent committed erythroid cell line, select MC genes were found to be occupied by NuRD, suggesting a direct mechanism of repression. Together, these observations suggest that a simple heritable silencing mechanism is insufficient to permanently repress MC genes. Instead, the continuous presence of GATA1, FOG1, and NuRD is required to maintain lineage fidelity throughout MK-erythroid ontogeny.
Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis
Authors: Lee Dae-Hoon , Zhou Li-Juan , Zhou Zheng , Xie Jian-Xin , Jung Ji-Ung , Liu Yu , Xi Cai-Xia , Mei Lin , Xiong Wen-Cheng
Published: January 2010

Neogenin, a deleted in colorectal cancer (DCC) family member, has been identified as a receptor for the neuronal axon guidance cues netrins and repulsive guidance molecules repulsive guidance molecules (RGM). RGMc, also called hemojuvelin (HJV), is essential for iron homeostasis. Here we provide evidence that neogenin plays a critical role in iron homeostasis by regulation of HJV secretion and bone morphogenetic protein (BMP) signaling. Livers of neogenin mutant mice exhibit iron overload, low levels of hepcidin, and reduced BMP signaling. Mutant hepatocytes in vitro show impaired BMP2 induction of Smad1/5/8 phosphorylation and hepcidin expression. Neogenin is expressed in liver cells in a reciprocal pattern to that of hepcidin, suggesting that neogenin functions in a cell nonautonomous manner. Further studies demonstrate that neogenin may stabilize HJV, a glycosylphosphatidylinositol-anchored protein that interacts with neogenin and suppresses its secretion. Taken together, our results lead the hypothesis that neogenin regulates iron homeostasis via inhibiting secretion of HJV, an inhibitor of BMP signaling, to enhance BMP signaling and hepcidin expression. These results reveal a novel mechanism underlying neogenin regulation of HJV-BMP signaling.
Haploinsufficiency of Apc leads to ineffective hematopoiesis
Authors: Wang Jianghong , Fernald Anthony A. , Anastasi John , Le Beau Michelle M. , Qian Zhijian
Published: January 2010

Loss of a whole chromosome 5 or a deletion of the long arm of chromosome 5, −5/del(5q), is a recurring abnormality in myeloid neoplasms. The APC gene is located at chromosome band 5q23, and is deleted in more than 95% of patients with a −5/del(5q), raising the question of whether haploinsufficiency of APC contributes to the development of myeloid neoplasms with loss of 5q. We show that conditional inactivation of a single allele of Apc in mice leads to the development of severe anemia with macrocytosis and monocytosis. Further characterization of the erythroid lineage revealed that erythropoiesis is blocked at the early stages of differentiation. The long-term hematopoietic stem cell (LT-HSC) and short-term HSC (ST-HSC) populations are expanded in Apc-heterozygous mice compared with the control littermates; however, the HSCs have a reduced capacity to regenerate hematopoiesis in vivo in the absence of a single allele of Apc. Apc heterozygous myeloid progenitor cells display an increased frequency of apoptosis, and decreased in vitro colony-forming capacity, recapitulating several characteristic features of myeloid neoplasms with a −5/del(5q). Our results indicate that haploinsufficiency of Apc impairs hematopoiesis, and raise the possibility that loss of function of APC contributes to the development of myelodysplasia.
BLAST-EXPLORER helps you building datasets for phylogenetic analysis
Authors: Dereeper Alexis , Audic Stephane , Claverie Jean-Michel , Blanc Guillaume
Published: January 2010

Background

The right sampling of homologous sequences for phylogenetic or molecular evolution analyses is a crucial step, the quality of which can have a significant impact on the final interpretation of the study. There is no single way for constructing datasets suitable for phylogenetic analysis, because this task intimately depends on the scientific question we want to address, Moreover, database mining softwares such as BLAST which are routinely used for searching homologous sequences are not specifically optimized for this task.

Results

To fill this gap, we designed BLAST-Explorer, an original and friendly web-based application that combines a BLAST search with a suite of tools that allows interactive, phylogenetic-oriented exploration of the BLAST results and flexible selection of homologous sequences among the BLAST hits. Once the selection of the BLAST hits is done using BLAST-Explorer, the corresponding sequence can be imported locally for external analysis or passed to the phylogenetic tree reconstruction pipelines available on the Phylogeny.fr platform.

Conclusions

BLAST-Explorer provides a simple, intuitive and interactive graphical representation of the BLAST results and allows selection and retrieving of the BLAST hit sequences based a wide range of criterions. Although BLAST-Explorer primarily aims at helping the construction of sequence datasets for further phylogenetic study, it can also be used as a standard BLAST server with enriched output. BLAST-Explorer is available at http://www.phylogeny.fr
Comparison of clastogen-induced gene expression profiles in wild-type and DNA repair-deficient Rad54/Rad54B cells
Authors: Mahabir Anuska G , Schaap Mirjam M , Pennings Jeroen LA , van Benthem Jan , Hendriksen Coenraad FM , van Steeg Harry
Published: January 2010

Background

Previously we found that Rad54/Rad54B cells are more sensitive towards mitomycin C (MMC) as compared to wild-type (WT) cells. This difference in sensitivity was absent upon exposure to other clastogens like bleomycin (BLM) and γ-radiation. In order to get further insight into possible underlying mechanisms, gene expression changes in WT and Rad54/Rad54B MEFs (mouse embryonic fibroblasts) after exposure to the clastogens MMC and BLM were investigated. Exposures of these cells to mutagens (N-ac-AAF and ENU) and vehicle were taken as controls.

Results

Most exposures resulted in an induction of DNA damage signaling and apoptosis genes and a reduced expression of cell division genes in cells of both genotypes. As expected, responses to N-ac-AAF were very similar in both genotypes. ENU exposure did not lead to significant gene expression changes in cells of both genotypes, presumably due to its short half-life. Gene expression responses to clastogens, however, showed a genotype-dependent effect for BLM and MMC. MMC treated Rad54/Rad54B MEFs showed no induction of p53-signaling, DNA damage response and apoptosis as seen for all the other treatments.

Conclusion

These data support our finding that different types of clastogens exist and that responses to these types depend on the DNA repair status of the cells.
AUF1 is involved in splenic follicular B cell maintenance
Authors: Sadri Navid , Lu Jin-Yu , Badura Michelle L , Schneider Robert J
Published: January 2010

Background

The adenosine/uridine-rich element (ARE)-binding protein AUF1 functions to regulate the inflammatory response through the targeted degradation of cytokine and other mRNAs that contain specific AREs in their 3' noncoding region (3' NCR). To investigate the role of AUF1 in the immune system, we characterized the lymphoid compartments of AUF1-deficient mice.

Results

Mice lacking AUF1 exhibit an altered proportion and size of splenic B cell subsets. We show prominent apoptosis in splenic B cell follicles and reduced expression of Bcl-2, A1, and Bcl-XLcorrelate with increased turnover and significant reduction in the number and proportion of splenic FO B cells in AUF1-deficient mice. In addition, AUF1-deficient mice exhibit a sharp decrease in splenic size and lymphocyte cellularity. Bone marrow transfer studies demonstrate that AUF1 deficiency induces cell-autonomous defects in mature B cell subsets but not in the overall number of splenocytes. Reconstitution of irradiated adult AUF1-deficient mice with wild-type bone marrow restores the proportion of FO and marginal zone (MZ) B cells, but does not rescue the decrease in the number of splenocytes. Functionally, AUF1-deficient mice mount an attenuated response to T cell-independent (TI) antigen, which correlates with impaired MZ B cell function.

Conclusion

These data indicate that AUF1 is important in the maintenance of splenic FO B cells and adequate humoral immune responses.
Dynamics of DNA methylation and Histone H4 acetylation during floral bud differentiation in azalea
Authors: Meijón Mónica , Feito Isabel , Valledor Luis , Rodríguez Roberto , Cañal María Jesús
Published: January 2010

Background

The ability to control the timing of flowering is a key strategy for planning production in ornamental species such as azalea, however it requires a thorough understanding of floral transition. Floral transition is achieved through a complex genetic network and regulated by multiple environmental and endogenous cues. Dynamic changes between chromatin states facilitating or inhibiting DNA transcription regulate the expression of floral induction pathways in response to environmental and developmental signals. DNA methylation and histone modifications are involved in controlling the functional state of chromatin and gene expression.

Results

The results of this work indicate that epigenetic mechanisms such as DNA methylation and histone H4 acetylation have opposite and particular dynamics during the transition from vegetative to reproductive development in the apical shoots of azalea. Global levels of DNA methylation and histone H4 acetylation as well as immunodetection of 5-mdC and acetylated H4, in addition to a morphological study have permitted the delimitation of four basic phases in the development of the azalea bud and allowed the identification of a stage of epigenetic reprogramming which showed a sharp decrease of whole DNA methylation similar to that is defined in other developmental processes in plants and in mammals.

Conclusion

The epigenetic control and reorganization of chromatin seem to be decisive for coordinating floral development in azalea. DNA methylation and H4 deacetylation act simultaneously and co-ordinately, restructuring the chromatin and regulating the gene expression during soot apical meristem development and floral differentiation.
Differential gene expression in incompatible interaction between wheat and stripe rust fungus revealed by cDNA-AFLP and comparison to compatible interaction
Authors: Wang Xiaojie , Liu Wei , Chen Xianming , Tang Chunlei , Dong Yanling , Ma Jinbiao , Huang Xueling , Wei Guorong , Han Qingmei , Huang Lili , Kang Zhensheng
Published: January 2010

Background

Stripe rust of wheat, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most important diseases of wheat worldwide. Due to special features of hexaploid wheat with large and complex genome and difficulties for transformation, and of Pst without sexual reproduction and hard to culture on media, the use of most genetic and molecular techniques in studying genes involved in the wheat-Pst interactions has been largely limited. The objective of this study was to identify transcriptionally regulated genes during an incompatible interaction between wheat and Pst using cDNA-AFLP technique

Results

A total of 52,992 transcript derived fragments (TDFs) were generated with 64 primer pairs and 2,437 (4.6%) of them displayed altered expression patterns after inoculation with 1,787 up-regulated and 650 down-regulated. We obtained reliable sequences (>100 bp) for 255 selected TDFs, of which 113 (44.3%) had putative functions identified. A large group (17.6%) of these genes shared high homology with genes involved in metabolism and photosynthesis; 13.8% to genes with functions related to disease defense and signal transduction; and those in the remaining groups (12.9%) to genes involved in transcription, transport processes, protein metabolism, and cell structure, respectively. Through comparing TDFs identified in the present study for incompatible interaction and those identified in the previous study for compatible interactions, 161 TDFs were shared by both interactions, 94 were expressed specifically in the incompatible interaction, of which the specificity of 43 selected transcripts were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Based on the analyses of homology to genes known to play a role in defense, signal transduction and protein metabolism, 20 TDFs were chosen and their expression patterns revealed by the cDNA-AFLP technique were confirmed using the qRT-PCR analysis.

Conclusion

We uncovered a number of new candidate genes possibly involved in the interactions of wheat and Pst, of which 11 TDFs expressed specifically in the incompatible interaction. Resistance to stripe rust in wheat cv. Suwon11 is executed after penetration has occurred. Moreover, we also found that plant responses in compatible and incompatible interactions are qualitatively similar but quantitatively different soon after stripe rust fungus infection.
Molecular modeling of the reductase domain to elucidate the reaction mechanism of reduction of peptidyl thioester into its corresponding alcohol in non-ribosomal peptide synthetases
Authors: Manavalan Balachandran , Murugapiran Senthil K , Lee Gwang , Choi Sangdun
Published: January 2010

Background

Nonribosomal peptide synthetases (NRPSs) are multienzymatic, multidomain megasynthases involved in the biosynthesis of pharmaceutically important nonribosomal peptides. The peptaibol synthetase from Trichoderma virens (TPS) is an important member of the NRPS family that exhibits antifungal properties. The majority of the NRPSs terminate peptide synthesis with the thioesterase (TE) domain, which either hydrolyzes the thioester linkage, releasing the free peptic acid, or catalyzes the intramolecular macrocyclization to produce a macrolactone product. TPS is an important NRPS that does not encompass a TE domain, but rather a reductase domain (R domain) to release the mature peptide product reductively with the aid of a NADPH cofactor. However, the catalytic mechanism of the reductase domain has not yet been elucidated.

Results

We present here a three-dimensional (3D) model of the reductase domain based on the crystal structure of vestitone reductase (VR). VR belongs to the short-chain dehydrogenase/reductase (SDR) superfamily and is responsible for the nicotinamide dinucleotide phosphate (NADPH)-dependent reduction of the substrate into its corresponding secondary alcohol product. The binding sites of the probable linear substrates, alamethicin, trichotoxin, antiamoebin I, chrysopermin C and gramicidin, were identified within the modeled R domain using multiple docking approaches. The docking results of the ligand in the active site of the R domain showed that reductase side chains have a high affinity towards ligand binding, while the thioester oxygen of each substrate forms a hydrogen bond with the OH group of Tyr176 and the thiol group of the substrate is closer to the Glu220. The modeling and docking studies revealed the reaction mechanism of reduction of thioester into a primary alcohol.

Conclusion

Peptaibol biosynthesis incorporates a single R domain, which appears to catalyze the four-electron reduction reaction of a peptidyl carrier protein (PCP)-bound peptide to its corresponding primary alcohol. Analysis of R domains present in the non-redundant (nr) database of the NCBI showed that the R domain always resides in the last NRPS module and is involved in either a two or four-electron reduction reaction.
Cost-effectiveness of human papillomavirus vaccination for prevention of cervical cancer in Taiwan
Authors: Liu Pang-Hsiang , Hu Fu-Chang , Lee Ping-Ing , Chow Song-Nan , Huang Chao-Wan , Wang Jung-Der
Published: January 2010

Background

Human papillomavirus (HPV) infection has been shown to be a major risk factor for cervical cancer. Vaccines against HPV-16 and HPV-18 are highly effective in preventing type-specific HPV infections and related cervical lesions. There is, however, limited data available describing the health and economic impacts of HPV vaccination in Taiwan. The objective of this study was to assess the cost-effectiveness of prophylactic HPV vaccination for the prevention of cervical cancer in Taiwan.

Methods

We developed a Markov model to compare the health and economic outcomes of vaccinating preadolescent girls (at the age of 12 years) for the prevention of cervical cancer with current practice, including cervical cytological screening. Data were synthesized from published papers or reports, and whenever possible, those specific to Taiwan were used. Sensitivity analyses were performed to account for important uncertainties and different vaccination scenarios.

Results

Under the assumption that the HPV vaccine could provide lifelong protection, the massive vaccination among preadolescent girls in Taiwan would lead to reduction in 73.3% of the total incident cervical cancer cases and would result in a life expectancy gain of 4.9 days or 8.7 quality-adjusted life days at a cost of US$324 as compared to the current practice. The incremental cost-effectiveness ratio (ICER) was US$23,939 per life year gained or US$13,674 per quality-adjusted life year (QALY) gained given the discount rate of 3%. Sensitivity analyses showed that this ICER would remain below US$30,000 per QALY under most conditions, even when vaccine efficacy was suboptimal or when vaccine-induced immunity required booster shots every 13 years.

Conclusions

Although gains in life expectancy may be modest at the individual level, the results indicate that prophylactic HPV vaccination of preadolescent girls in Taiwan would result in substantial population benefits with a favorable cost-effectiveness ratio. Nevertheless, we should not overlook the urgency to improve the compliance rate of cervical screening, particularly for older individuals.