bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Organizational Characteristics and Human Capital Endowments on Pay of Female and Male Middle School Principals
Authors: Young Phillip , Reimer Don , Young Karen Holsey
Published: August 2010

Background: Studies addressing pay discrimination for females in education have relied on main effect regression models, mostly examining amount (intercept values) rather than rate of pay (slope coefficients). Purpose: The purpose is to determine if organizational characteristics and human capital endowments purported to influence pay are facially neutral (amount of pay) or have a disproportional impact (rate of pay) for female middle school principals. Setting: The population is all California public middle school principals, who are stratified by sex and randomly selected through a sampling process that includes only a single principal from any school district. Research Design: A hierarchical regression design is used to assess main effects for organizational characteristics and human capital variables (amount) and interaction effects (rate) of these variables and a residual effect for sex. Data Collection: Organizational characteristics for school districts and school buildings were obtained from a state database, and human capital endowments and information for pay were assessed via survey self-reports of principals. Findings: Organizational and human capital variables are facially neutral and account for substantial variance in pay amount ( R2 = .44, p ≤ .01). None of the interaction terms (Δ R2 = .02, p ≥ .05) reflect a disproportional impact (rate of pay) for females, and the residual sex coefficient is nonsignificant (Δ R2 = .00, p ≥ .05). Conclusions: These findings differ from existing research suggesting pay discrimination on the basis of sex at the school building level but may do so because of methodological advancements and/or a temporal effect.
The Effects of Small Sample Size on Identifying Polytomous DIF Using the Liu–Agresti Estimator of the Cumulative Common Odds Ratio
Authors: Carvajal Jorge , Skorupski William P.
Published: August 2010

This study is an evaluation of the behavior of the Liu—Agresti estimator of the cumulative common odds ratio when identifying differential item functioning (DIF) with polytomously scored test items using small samples. The Liu—Agresti estimator has been proposed by Penfield and Algina as a promising approach for the study of polytomous DIF but no simulation study focusing on small samples has analyzed this estimator regarding effect size, Type I error, and power rates. The article begins with a description of this estimator in the context of polytomous DIF. Then it presents the methods and results for a simulation study in which three factors are manipulated: between-group difference in ability distribution, form of DIF introduced into the polytomous item, and sample size. The results of this study indicate that for samples smaller than 200, very little power was observed for statistical significance testing; however, Type I error rates were close to nominal levels, and the recovery of the log odds ratio as an effect size was relatively unaffected by sample size for high discriminating items. Implications for practice are discussed.
Prediction of drape profile of cotton woven fabrics using artificial neural network and multiple regression method
Authors: Ajit Kumar Pattanayak  , Luximon Ameersing , Khandual Asimananda
Published: August 2010

Fabric drape is one of the most important factors which affect the graceful appearance of the garment. The drape coefficient is the widely used parameter to describe fabric drape but it needs other parameters to explain the fabric behavior. In this study, we have investigated the relationship between the fabric drape parameters such as drape coefficient, drape distance ratio, fold depth index, amplitude and number of nodes and low stress mechanical properties. Drape parameters were tested on a specially developed instrument based on a digital image processing technique and the low stress mechanical properties were tested by the Kawabata evaluation system. Then the drape parameters were predicted by constructing models using multiple regressions method and feed-forward back-propagation neural network technique. Simple equations are derived using regressions method to predict the five shape parameters of drape profile from the low stress mechanical properties. It is observed that bending, shear and aerial density affect the drape parameters most whereas the tensile and compression have little effect on the drape parameters.
Physical Activity Preferences and Type 2 Diabetes
Authors: Forbes Cynthia C. , Plotnikoff Ronald C. , Courneya Kerry S. , Boulé Normand G.
Published: August 2010

Purpose

The purpose of this study was to examine physical activity counseling and program preferences in a sample of adults with type 2 diabetes. Specifically, the objectives were to determine physical activity preferences (objective 1), and whether there were any significant differences between age and/or sex groups for these preferences (objective 1a). A subsidiary objective was to explore potential associations of key social-cognitive constructs (ie, self-efficacy and social support) with physical activity preferences (objective 2).

Methods

This exploratory study consisted of a quantitative, secondary analysis of survey data from a national sample of adults with type 2 diabetes (N = 244). A qualitative follow-up employing telephone interviews was conducted with 14 individuals.

Results

Consistent with hypotheses, walking was the most preferred physical activity behavior and there was a preference for engaging in physical activity with others. There were significant (P values < .05) differences in counseling and program preferences between demographic (age and sex), and physical activity cognitive scores. For example, a significantly (P < .05) higher physical activity intensity preference was found in men and younger participants.

Conclusions

Tailoring interventions and physical activity programs to the specific preferences of individuals is an important component for health professionals and researchers in facilitating this behavior.
Engaging Marketing Students: Student Operated Businesses in a Simulated World
Authors: Russell-Bennett Rebekah , Rundle-Thiele Sharyn R. , Kuhn Kerri-Ann
Published: August 2010

Engaged students are committed and more likely to continue their university studies. Subsequently, they are less resource intensive from a university’s perspective. This article details an experiential second-year marketing course that requires students to develop real products and services to sell on two organized market days. In the course, students participate as both consumers and marketers in a simulated world. The current article explores the effectiveness of this experiential assessment in terms of its ability to engage students. Comparing student engagement to a traditional lecture course and National Survey of Student Engagement benchmarks, the results suggest that the use of a simulated marketplace is capable of engaging students. Specifically, the assessment reported encourages more active learning and collaboration, is more academically challenging, and permits more student—faculty interaction than a traditional lecture-based course. The course structure outlined in this article permits the dynamics of a live marketing environment to be introduced into the classroom. The authors provide practical advice for educators seeking to design and implement engaging pedagogy.
Effect of tannin on flexural properties of phenol formaldehyde glycerol reinforced composites: preliminary results
Authors: Cardona F. , Ku H. , Chouzenoux L.
Published: August 2010

Phenol formaldehyde composites are modified with glycerol—tannin mixes with varying percentages by weight of phenolic resin to glycerol—tannin. The glycerol-to-tannin ratio is also varied. In this study also, different percentages by weight of SLG (a commercial ceramic microsphere) are added to the composites. The effect of glycerol—tannin mix and added SLG on the flexural properties was studied. It was found that the flexural stress decreases gradually with increasing tannin when there is no SLG. With SLG, the presence of tannin in the composites reduces the flexural stress drastically. Tannin reduces the strain at break. With SLG, this reduction of the yield strain is more apparent. Tannin increases the flexural modulus of the composite and SLG acts in the opposite direction. The use of tannin in the phenolic composites improves the ‘green’ character of the composite materials. It was also found that the presence of tannin made the mixing of phenolic resins with glycerol easier.
Lifelong Learning as Being: The Heideggerian Perspective
Authors: Su Ya-hui
Published: August 2010

This article contends that the development of lifelong learning needs to be grounded within the framework of being, a concept inspired by Heidegger, rather than within the framework of having. This article also describes the problems of the adult education literature, which favors the pragmatic sense of being and, thus, may undertheorize the meanings of developing lifelong learning. It considers Heidegger’s conception of “being” by defining the existential mode of learning as part of the development of lifelong learning, thereby resisting the exclusive mention of the functional mode of learning in times of postmodern change. The analysis of being is captured by the language of dynamic movement, which grants no priority to one’s thought, action, or feeling, none of whose operations can be understood without reference to the other. Finally, the implications of the being mode of learning for developing adult education research, practice, and policy are discussed.
A Methodological Review of Research on Leadership Development and Social Capital: Is There a Cause and Effect Relationship?
Authors: Van De Valk Lawrence J. , Constas Mark A.
Published: August 2010

Recent interest in studying social aspects of leadership has brought attention to the relationship between leadership and social capital. There is also growing interest among stakeholders (researchers, practitioners, funders, and program participants) to improve evaluation methods for leadership development programs (LDPs). The purpose of the present review is to determine the extent to which recent LDP evaluation efforts can support a causal assertion that participation in an LDP enhances an individual’s or group’s social capital. Although they do not dispute that a relationship between leadership and social capital exists, using basic requirements for causal inference described by Shadish, Cook, and Campbell, the authors conclude that the existing literature does not support a causal inference that participation in an LDP necessarily enhances social capital. The limited corpus of work reviewed in this article is indicative of the dearth of scholarly writing on the matter of leadership development efforts and causal inference.
Everyday Scholars: Framing Informal Learning in Terms of Academic Disciplines and Skills
Authors: Jubas Kaela
Published: August 2010

This article discusses shopping, especially critical shopping, as a process of informal and incidental adult learning about the intersecting politics of globalization and consumption. The author uses academic skills and disciplines as a metaphor to respond to an emerging conceptual question: To what extent can formality, informality, and incidentalism be seen as aspects of adult learning? The author conceptualizes learning as a holistic process, with emotional, spiritual, and intellectual dimensions, and identifies five themes that illustrate how the multidimensional learning in an everyday process such as shopping incorporates all three aspects. These themes are referred to as learning to learn, learning to do research, learning to develop a philosophy of shopping, learning to build a shopping-related literacy, and learning to construct a shopper’s geography. This metaphor helps convey the depth and breadth of everyday learning and blur the conceptual distinction between formal and informal or incidental learning.
Whiteness as Property: Predatory Lending and the Reproduction of Racialized Inequality
Authors: Beeman Angie , Silfen Glasberg Davita , Casey Colleen
Published: August 2010

With the recent economic crisis in the USA, stories of homes lost to foreclosure are increasingly common. In this paper, we attempt to connect this present day problem to its historical roots in racial oppression. We examine 2004 data from the Home Mortgage Disclosure Act database for racial disparities in lending. We find that African Americans are less likely than European Americans to receive loans from regulated lenders. We also find that regardless of lender type and income level, African Americans are more likely than European Americans to receive high priced loans. We argue that these racial differences in access to quality loans that allow for the acquisition of assets through home ownership are part of a historical trend of whiteness as property and undeserved enrichment and unjust impoverishment.
Broker Fixed: The Racialized Social Structure and the Subjugation of Indigenous Populations in the Andes
Authors: Scarritt Arthur
Published: August 2010

Responding to calls to return racial analysis to indigenous Latin America, this article moves beyond the prejudicial attitudes of dominant groups to specify how native subordination gets perpetuated as a normal outcome of the organization of society. I argue that a naturalized system of indirect rule racially subordinates native populations through creating the position of mestizo ‘authoritarian intermediary’. Natives must depend on these cultural brokers for their personhood, while maintaining this privileged position requires facilitating indigenous exploitation. Institutional structures combine with cultural practices to generate a vicious cycle in which increased village intermediary success increases native marginalization. This racialized social structure explains my ethnographic findings that indigenous villagers continued to support the same coterie of mestizos despite their regular and sometimes extreme acts of peculation. My findings about the primacy of race suggest new directions for research into indigenous studies, ethnic mobilizations, and the global dimensions of racial domination.
Nutritional Symptom and Body Composition Outcomes of Aerobic Exercise in Women With Breast Cancer
Authors: DeNysschen Carol A. , Brown Jean K. , Cho Maria H. , Dodd Marylin J.
Published: August 2010

The purpose of this secondary analysis was to examine the nutritional symptoms and body composition outcomes of aerobic exercise in women with breast cancer. A single-blind clinical trial, randomized to tailored Pro-Self© exercise during and after chemotherapy, after chemotherapy only, or no Pro-Self (usual care). One hundred women, average age 49.9 years ( SD = 9.6), participated. Mild taste changes, nausea, constipation, and anorexia were experienced by 47% to 55% at baseline and end of treatment but diminished post treatment. No group differences were found in total nutritional symptoms or symptom severity. Intervention group participants maintained lean body mass; control group participants had nonsignificant lean body mass loss. Issues related to self-report, protocol adherence, and generalizability limit findings. Aerobic exercise is useful in achieving healthy weight and body composition, but the intensity and duration achieved during cancer treatment and recovery did not produce significant changes.
Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis
Authors: Jafari Naghmeh , Broer Linda , Hoppenbrouwers Ilse A , van Duijn Cornelia M , Hintzen Rogier Q
Published: August 2010

Background: Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism.

Objectives: Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis.

Methods: Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501.

Results: HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10 -5). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 ( p = 0.003) for HLA-A.

Conclusions: HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.
A method for evaluating treatment switching criteria in multiple sclerosis
Authors: Healy Brian C , Glanz Bonnie I , Stankiewicz James , Buckle Guy , Weiner Howard , Chitnis Tanuja
Published: August 2010

Background and Objective: We investigated a method to evaluate a treatment switching approach, namely treatment change after one multiple sclerosis (MS) relapse.

Methods: Patients who experienced a relapse while on a first-line disease-modifying therapy, glatiramer acetate, were identified. Based on their subsequent course, patients were divided into two groups: those who changed treatment and those who did not. Patients were allowed to change to any other treatment. Subsequent annualized relapse rate and time to next relapse were compared in the two groups. Since patients were not randomized to treatment group, negative binomial and Cox regression models were used to control for several potential clinical confounders, including relapse severity, relapse duration, age, disease duration and presence of previous/combination therapy. In addition, an inverse probability of treatment weighting model was used to control for confounding. Several secondary analyses investigated patient subgroups.

Results: Statistical modeling showed that there was no significant difference between groups in terms of relapse rate (rate ratio; 95% CI = 0.68; 0.35, 1.31) and time to next relapse (hazard ratio; 95% CI = 0.61; 0.30, 1.25). All secondary analyses confirmed these results. In addition, no significant difference in time to sustained progression on the Expanded Disability Status Scale was observed ( p > 0.05). Our approach allowed investigation of the choice to change treatment after a relapse. Conclusions: Our results showed that a single relapse may not be sufficient to indicate treatment failure. Although clinical confounders were addressed in our modeling, unmeasured confounders, particularly the presence of magnetic resonance imaging activity, may have biased our conclusion.
Prevalence of Fungi in Indoor Air with Reference to Gymnasiums with Swimming Pools
Authors: Viegas Carla , Alves Célia , Carolino Elisabete , Rosado Laura , Silva Santos Carlos
Published: August 2010

Fungal contamination of air in 10 gymnasiums with swimming pools was monitored. Fifty air samples of 200L each were collected, using a Millipore air tester, from the area surrounding the pool, in training studios, in showers and changing rooms for both sexes, and also, outside premises, since these are the places regarded as reference. Simultaneously, environmental parameters — temperature and humidity — were also monitored. Some 25 different species of fungi were identified. The six most commonly isolated genera were the following: Cladosporium sp. (36.6%), Penicillium sp. (19.0%), Aspergillus sp. (10.2%), Mucor sp. (7%), Phoma sp. and Chrysonilia sp. (3.3%). For yeasts, three different genera were identified, namely, Rhodotorula sp. (70%), Trichosporon mucoides and Crypto-coccus uniguttulattus (10%).
A Review of Food Allergy and Nutritional Considerations in the Food-Allergic Adult
Authors: O'Neil Carol E. , Zanovec Michael , Nicklas Theresa A.
Published: August 2010

In the United States, the prevalence of adults with food allergies is approximately 2% to 3%. Theoretically, any food can cause an allergic reaction; however, some foods are clearly more allergenic than others. In adults, peanuts, tree nuts, finned fish, crustaceans, fruit, and vegetables account for 85% of the food-allergic reactions. Currently, the only ways to manage food allergies are to avoid the allergen and initiate therapy for an allergic reaction if ingestion does occur. The presence of homologous proteins among animal or plant foods and between foods and certain airborne allergens may account for cross-sensitization that may be clinically relevant. For inpatients or outpatients with food allergies, nutrient and fluid requirements are the same as for individuals without food allergies. Since patients with adverse reactions to food may self-restrict intake or have been counseled on food avoidance, it is particularly important to determine dietary adequacy and to provide patients with appropriate food substitutions to provide nutrients that may be missing from a patient’s diet. This is of particular concern for individuals with multiple food allergies. Eating away from home and traveling also pose special problems for those with food allergies.
Combining Lifestyle Medicine With Medication Therapy Management Services in a Community Pharmacy Setting
Authors: Lenz Thomas L.
Published: August 2010

Medication therapy management (MTM) services have been performed by pharmacists to optimize the therapeutic outcomes of patients for nearly 10 years. To date, few pharmacists have incorporated lifestyle medicine practices with traditional MTM services to more optimally manage and prevent chronic conditions. This article describes one community pharmacy-based program that incorporates lifestyle medicine with traditional MTM services. The tools used to conduct the program are also provided along with a brief description of the outcomes after the first year of the program. Pharmacists are well positioned within the community to promote lifestyle medicine. Incorporating these services into MTM programs is an excellent way for pharmacists to provide a high level of care to patients with chronic conditions.
Robotic-assisted laparoscopic mesh sacrocolpopexy
Authors: Gilleran Jason P. , Johnson Matthew , Hundley Andrew
Published: August 2010

The current ‘gold standard’ surgical repair for apical prolapse is the abdominal mesh sacrocolpopexy. Use of a robotic-assisted laparoscopic surgical approach has been demonstrated to be feasible as a minimally invasive approach and is gaining popularity amongst pelvic floor reconstructive surgeons. Although outcome data for robotic-assisted sacrocolpopexy (RASC) is only just emerging, several small series have demonstrated anatomic and functional outcomes, as well as complication rates, comparable to those reported for open surgery. The primary advantages thus far for RASC over open surgery include decreased blood loss and shorter hospital stay.
The role of Interleukin 6 in the pathophysiology of rheumatoid arthritis
Authors: Srirangan Srinivasan , Choy Ernest H.
Published: August 2010

Interleukin 6 (IL-6) is a pleiotropic cytokine with a pivotal role in the pathophysiology of rheumatoid arthritis (RA). It is found in abundance in the synovial fluid and serum of patients with RA and the level correlates with the disease activity and joint destruction. IL-6 can promote synovitis and joint destruction by stimulating neutrophil migration, osteoclast maturation and vascular endothelial growth factor (VEGF)-stimulated pannus proliferation. IL-6 may also be mediating many of the systematic manifestations of RA including inducing the acute-phase reaction [including C-reactive protein (CRP)], anaemia through hecipidin production, fatigue via the hypothalmic-pituitary-adrenal (HPA) axis) and osteoporosis from its effect on osteoclasts. In addition, IL-6 may contribute to the induction and maintenance of the autoimmune process through B-cell maturation and TH-17 differentiation. All of the above makes IL-6 blockade a desirable therapeutic option in the treatment of RA. Following successful animal studies, a humanized anti-interleukin-6 receptor (anti-IL-6R) monoclonal antibody, tocilizumab (TCZ), entered into clinical trials and it has been shown to be an effective treatment in several large phase III clinical trials in RA with rapid and sustained improvement in disease activity, reducing radiographic joint damage and improving physical function.
Current aspects of pathogenesis in Sjögren’s syndrome
Authors: Voulgarelis Michael , Tzioufas Athanasios G.
Published: August 2010

Sjögren’s syndrome is a chronic autoimmune process that primarily affects the exocrine glands and leads to their functional impairment. The exocrine gland involvement is characterized by a focal, mononuclear cell infiltrate which is accumulated around ducts and, in some patients, extends and replaces the secretory functional units. The mechanisms of this autoimmune ‘exocrinopathy’ are not fully understood. The immune attack that follows activation or apoptosis of glandular epithelial cells exposing autoantigens in genetically predisposed individuals may drive the immune-mediated tissue injury. Abnormalities related to the upregulation of type I interferon-regulated genes (interferon signature), abnormal expression of B-cell-activating factor (BAFF) and activation of the IL-23/TH17 pathway are among the immune mediators implicated in the pathogenesis of autoimmune lesions within the salivary glands. Such abnormalities demonstrate the complex interplay between innate and adaptive immunity that contributes to autoimmune ‘exocrinopathy’.
Periodization
Authors: Lorenz Daniel S. , Reiman Michael P. , Walker John C.
Published: August 2010

Background:

Clinicians are constantly faced with the challenge of designing training programs for injured and noninjured athletes that maximize healing and optimize performance. Periodization is a concept of systematic progression—that is, resistance training programs that follow predictable patterns of change in training variables. The strength training literature is abundant with studies comparing periodization schemes on uninjured, trained, and untrained athletes. The rehabilitation literature, however, is scarce with information about how to optimally design resistance training programs based on periodization principles for injured athletes. The purpose of this review is to discuss relevant training variables and methods of periodization, as well as periodization program outcomes. A secondary purpose is to provide an anecdotal framework regarding implementation of periodization principles into rehabilitation programs.

Evidence Acquisition:

A Medline search from 1979 to 2009 was implemented with the keywords periodization, strength training, rehabilitation, endurance, power, hypertrophy, and resistance training with the Boolean term AND in all possible combinations in the English language. Each author also undertook independent hand searching of article references used in this review.

Results:

Based on the studies researched, periodized strength training regimens demonstrate improved outcomes as compared to nonperiodized programs.

Conclusions:

Despite the evidence in the strength training literature supporting periodization programs, there is a considerable lack of data in the rehabilitation literature about program design and successful implementation of periodization into rehabilitation programs.
Good Intentions, Optimistic Self-Predictions, and Missed Opportunities
Authors: Koehler Derek J. , White Rebecca J. , John Leslie K.
Published: August 2010

Self-predictions are highly sensitive to current intentions but often largely insensitive to factors influencing the readiness with which those intentions are translated into future behavior. When such factors are under a person’s control, they could be used to increase the probability that desired future behavior will be undertaken, but they will be underused if self-predictions underestimate their impact. This hypothesis was borne out in two experiments involving working students attempting to achieve a savings goal: They strongly intended to save, made overly optimistic self-predictions even when it was costly to do so, and were willing to pay very little for a service that could help them save more because they did not anticipate its impact on their future behavior. By contrast, students who were informed of the service’s actual impact were willing to pay more for it, and students did not underestimate the impact of the service on fellow students.
Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL
Authors: Ott German , Ziepert Marita , Klapper Wolfram , Horn Heike , Szczepanowski Monika , Bernd Heinz-Wolfram , Thorns Christoph , Feller Alfred C. , Lenze Dido , Hummel Michael , Stein Harald , Müller-Hermelink Hans-Konrad , Frank Matthias , Hansmann Martin-Leo , Barth Thomas F. E. , Möller Peter , Cogliatti Sergio , Pfreundschuh Michael , Schmitz Norbert , Trümper Lorenz , Loeffler Markus , Rosenwald Andreas
Published: August 2010

The survival of diffuse large B-cell lymphoma patients varies considerably, reflecting the molecular diversity of tumors. In view of the controversy whether cytologic features, immunohistochemical markers or gene expression signatures may capture this molecular diversity, we investigated which features provide prognostic information in a prospective trial in the R-CHOP treatment era. Within the cohort of DLBCLs patients treated in the RICOVER-60 trial of the German High-Grade Lymphoma Study Group (DSHNHL), we tested the prognostic impact of IB morphology in 949 patients. The expression of immunohistochemical markers CD5, CD10, BCL2, BCL6, human leukocyte antigen (HLA)–DR, interferon regulatory factor-4/multiple myeloma-1 (IRF4/MUM1), and Ki-67 was assessed in 506 patients. Expression of the immunohistochemical markers tested was of modest, if any, prognostic relevance. Moreover, the Hans algorithm using the expression patterns of CD10, BCL6, and interferon regulatory factor-4/multiple myeloma-1 failed to show prognostic significance in the entire cohort as well as in patient subgroups. IB morphology, however, emerged as a robust, significantly adverse prognostic factor in multivariate analysis, and its diagnosis showed a good reproducibility among expert hematopathologists. We conclude, therefore, that IB morphology in DLBCL is likely to capture some of the adverse molecular alterations that are currently not detectable in a routine diagnostic setting, and that its recognition has significant prognostic power.
EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis
Authors: Velichutina Irina , Shaknovich Rita , Geng Huimin , Johnson Nathalie A. , Gascoyne Randy D. , Melnick Ari M. , Elemento Olivier
Published: August 2010

EZH2 is the catalytic subunit of the PRC2 Polycomb complex and mediates transcriptional repression through its histone methyltransferase activity. EZH2 is up-regulated in normal germinal center (GC) B cells and is implicated in lymphomagenesis. To explore the transcriptional programs controlled by EZH2, we performed chromatin immunoprecipitation (ChIP-on-chip) in GC cells and found that it binds approximately 1800 promoters, often associated with DNA sequences similar to Droso-phila Polycomb response elements. While EZH2 targets overlapped extensively between GC B cells and embryonic stem cells, we also observed a large GC-specific EZH2 regulatory program. These genes are preferentially histone 3 lysine 27–trimethylated and repressed in GC B cells and include several key cell cycle–related tumor suppressor genes. Accordingly, siRNA-mediated down-regulation of EZH2 in diffuse large B-cell lymphoma (DLBCL) cells resulted in acute cell cycle arrest at the G1/S transition and up-regulation of its tumor suppressor target genes. At the DNA level, EZH2-bound promoters are hypomethylated in GC B cells, but many of them are aberrantly hypermethylated in DLBCL, suggesting disruption of normal epigenetic processes in these cells. EZH2 is thus involved in regulating a specific epigenetic program in normal GCs, including silencing of antiproliferative genes, which may contribute to the malignant transformation of GC B cells into DLBCLs.
The requirement for NKG2D in NK cell–mediated rejection of parental bone marrow grafts is determined by MHC class I expressed by the graft recipient
Authors: Beilke Joshua N. , Benjamin Jonathan , Lanier Lewis L.
Published: August 2010

Natural killer (NK) cells provide a unique barrier to semiallogeneic bone marrow (BM) transplantation. In the setting where the parents donate to the F1 offspring, rejection of parental bone marrow occurs. This “hybrid resistance” is completely NK cell dependent, as T cells in the F1 recipient tolerate parental grafts. Previously, we demonstrated that rejection of BALB/c parental BM by (BALB/c × C57BL/6) F1-recipient NK cells is dependent on the NKG2D-activating receptor, whereas rejection of parental C57BL/6 BM does not require NKG2D. BALB/c and B6 mice possess different NKG2D ligand genes and express these ligands differently on reconstituting BM cells. Herein, we show that the requirement for NKG2D in rejection depends on the major histocompatibility complex haplotype of donor cells and not the differences in the expression of NKG2D ligands. NKG2D stimulation of NK cell–mediated rejection was required to overcome inhibition induced by H-2Dd when it engaged an inhibitory Ly49 receptor, whereas rejection of parental BM expressing the ligand, H-2Kb, did not require NKG2D. Thus, interactions between the inhibitory receptors on F1 NK cells and parental major histocompatibility complex class I ligands determine whether activation via NKG2D is required to achieve the threshold for rejection of parental BM grafts.
Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance
Authors: Moreno Carol , Hodgson Kate , Ferrer Gerardo , Elena Montse , Filella Xavier , Pereira Arturo , Baumann Tycho , Montserrat Emili
Published: August 2010

We analyzed prevalence, characteristics, clinical correlates, and prognostic significance of autoimmune cytopenia in patients with chronic lymphocytic leukemia. Seventy of 960 unselected patients (7%) had autoimmune cytopenia, of whom 19 were detected at diagnosis, 3 before diagnosis, and 48 during the course of the disease. Forty-nine patients had autoimmune hemolytic anemia, 20 had immune thrombocytopenic purpura, and 1 had both conditions. A clear association was observed between autoimmune cytopenia and poor prognostic variables (ie, high blood lymphocyte count, rapid blood lymphocyte doubling time, increased serum β-2 microglobulin level, and high expression of ζ-associated protein 70 and CD38). Nevertheless, the outcome of patients with autoimmune cytopenia as a whole was not significantly different from that of patients without this complication. Furthermore, no differences were observed according to time at which cytopenia was detected (ie, at diagnosis, during course of disease). Importantly, patients with advanced (Binet stage C) disease because of an autoimmune mechanism had a significantly better survival than patients in advanced stage related to a massive bone marrow infiltration (median survivals: 7.4 years vs 3.7 years; P = .02). These results emphasize the importance of determining the origin of cytopenia in patients with chronic lymphocytic leukemia for both treatment and prognostic purposes.
Protease-activated receptors mediate crosstalk between coagulation and fibrinolysis
Authors: McEachron Troy A. , Pawlinski Rafal , Richards Kristy L. , Church Frank C. , Mackman Nigel
Published: August 2010

The coagulation and fibrinolytic systems contribute to malignancy by increasing angiogenesis, tumor growth, tumor invasion, and tumor metastasis. Oncogenic transformation increases the expression of tissue factor (TF) that results in local generation of coagulation proteases and activation of protease-activated receptor (PAR)-1 and PAR-2. We compared the PAR-dependent expression of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI)-1 in 2 murine mammary adencocarcinoma cell lines: metastatic 4T1 cells and nonmetastatic 67NR cells. 4T1 cells expressed TF, PAR-1 and PAR-2 whereas 67NR cells expressed TF and PAR-1. We also silenced PAR-1 or PAR-2 expression in the 4T1 cells. We discovered 2 distinct mechanisms for PAR-dependent expression of uPA and PAI-1. First, we found that factor Xa or thrombin activation of PAR-1 led to a rapid release of stored intracellular uPA into the culture supernatant. Second, thrombin transactivation of a PAR-1/PAR-2 complex resulted in increases in PAI-1 mRNA and protein expression. Cells lacking PAR-2 failed to express PAI-1 in response to thrombin and factor Xa did not activate the PAR-1/PAR-2 complex. Our results reveal how PAR-1 and PAR-2 on tumor cells mediate crosstalk between coagulation and fibrinolysis.
Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome
Authors: Carmona-Mora Paulina , Encina Carolina A , Canales Cesar P , Cao Lei , Molina Jessica , Kairath Pamela , Young Juan I , Walz Katherina
Published: August 2010

Background

Smith-Magenis Syndrome is a contiguous gene syndrome in which the dosage sensitive gene has been identified: the Retinoic Acid Induced 1 (RAI1). Little is known about the function of human RAI1.

Results

We generated the full-length cDNA of the wild type protein and five mutated forms: RAI1-HA 2687delC, RAI1-HA 3103delC, RAI1 R960X, RAI1-HA Q1562R, and RAI1-HA S1808N. Four of them have been previously associated with SMS clinical phenotype. Molecular weight, subcellular localization and transcription factor activity of the wild type and mutant forms were studied by western blot, immunofluorescence and luciferase assays respectively. The wild type protein and the two missense mutations presented a higher molecular weight than expected, localized to the nucleus and activated transcription of a reporter gene. The frameshift mutations generated a truncated polypeptide with transcription factor activity but abnormal subcellular localization, and the same was true for the 1-960aa N-terminal half of RAI1. Two different C-terminal halves of the RAI1 protein (1038aa-end and 1229aa-end) were able to localize into the nucleus but had no transactivation activity.

Conclusion

Our results indicate that transcription factor activity and subcellular localization signals reside in two separate domains of the protein and both are essential for the correct functionality of RAI1. The pathogenic outcome of some of the mutated forms can be explained by the dissociation of these two domains.
Hydroxysafflor Yellow A protects spinal cords from ischemia/reperfusion injury in rabbits
Authors: Shan Le-qun , Ma Sai , Qiu Xiu-chun , Zhou Yong , Zhang Yong , Zheng Lian-he , Ren Peng-cheng , Wang Yu-cai , Fan Qing-yu , Ma Bao-an
Published: August 2010

Background

Hydroxysafflor Yellow A (HSYA), which is one of the most important active ingredients of the Chinese herb Carthamus tinctorius L, is widely used in the treatment of cerebrovascular and cardiovascular diseases. However, the potential protective effect of HSYA in spinal cord ischemia/reperfusion (I/R) injury is still unknown.

Methods

Thirty-nine rabbits were randomly divided into three groups: sham group, I/R group and HSYA group. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, biochemical analysis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining.

Results

Neurological outcomes in HSYA group were slightly improved compared with those in I/R group. Histopathological analysis revealed that HSYA treatment attenuated I/R induced necrosis in spinal cords. Similarly, alleviated oxidative stress was indicated by decreased malondialdehyde (MDA) level and increased superoxide dismutase (SOD) activity after HSYA treatment. Moreover, as seen from TUNEL results, HSYA also protected neurons from I/R-induced apoptosis in rabbits.

Conclusions

These findings suggest that HSYA may protect spinal cords from I/R injury by alleviating oxidative stress and reducing neuronal apoptosis in rabbits.
Identification of transcriptome induced in roots of maize seedlings at the late stage of waterlogging
Authors: Zou Xiling , Jiang Yuanyuan , Liu Lei , Zhang Zuxin , Zheng Yonglian
Published: August 2010

Background

Plants respond to low oxygen stress, particularly that caused by waterlogging, by altering transcription and translation. Previous studies have mostly focused on revealing the mechanism of the response at the early stage, and there is limited information about the transcriptional profile of genes in maize roots at the late stage of waterlogging. The genetic basis of waterlogging tolerance is largely unknown. In this study, the transcriptome at the late stage of waterlogging was assayed in root cells of the tolerant inbred line HZ32, using suppression subtractive hybridization (SSH). A forward SSH library using RNA populations from four time points (12 h, 16 h, 20 h and 24 h) after waterlogging treatment was constructed to reveal up-regulated genes, and transcriptional and linkage data was integrated to identify candidate genes for waterlogging tolerance.

Results

Reverse Northern analysis of a set of 768 cDNA clones from the SSH library revealed a large number of genes were up-regulated by waterlogging. A total of 465 ESTs were assembled into 296 unigenes. Bioinformatic analysis revealed that the genes were involved in complex pathways, such as signal transduction, protein degradation, ion transport, carbon and amino acid metabolism, and transcriptional and translational regulation, and might play important roles at the late stage of the response to waterlogging. A significant number of unigenes were of unknown function. Approximately 67% of the unigenes could be aligned on the maize genome and 63 of them were co-located within reported QTLs.

Conclusion

The late response to waterlogging in maize roots involves a broad spectrum of genes, which are mainly associated with two response processes: defense at the early stage and adaption at the late stage. Signal transduction plays a key role in activating genes related to the tolerance mechanism for survival during prolonged waterlogging. The crosstalk between carbon and amino acid metabolism reveals that amino acid metabolism performs two main roles at the late stage: the regulation of cytoplasmic pH and energy supply through breakdown of the carbon skeleton.
Seroepidemiology of pandemic influenza A (H1N1) 2009 virus infections in Pune, India
Authors: Tandale Babasaheb V , Pawar Shailesh D , Gurav Yogesh K , Chadha Mandeep S , Koratkar Santosh S , Shelke Vijay N , Mishra Akhilesh C
Published: August 2010

Background

In India, Pune was one of the badly affected cities during the influenza A (H1N1) 2009 pandemic. We undertook serosurveys among the risk groups and general population to determine the extent of pandemic influenza A (H1N1) 2009 virus infections.

Methods

Pre-pandemic sera from the archives, collected during January 2005 to March 2009, were assayed for the determination of baseline seropositivity. Serosurveys were undertaken among the risk groups such as hospital staff, general practitioners, school children and staff and general population between 15th August and 11th December 2009. In addition, the PCR-confirmed pandemic influenza A (H1N1) 2009 cases and their household contacts were also investigated. Haemagglutination-inhibition (HI) assays were performed using turkey red blood cells employing standard protocols. A titre of ≥1:40 was considered seropositive.

Results

Only 2 (0.9%) of the 222 pre-pandemic sera were positive. The test-retest reliability of HI assay in 101 sera was 98% for pandemic H1N1, 93.1% for seasonal H1N1 and 94% for seasonal H3N2. The sera from 48 (73.8%) of 65 PCR-confirmed pandemic H1N1 cases in 2009 were positive. Seropositivity among general practitioners increased from 4.9% in August to 9.4% in November and 15.1% in December. Among hospital staff, seropositivity increased from 2.8% in August to 12% in November. Seropositivity among the schools increased from 2% in August to 10.7% in September. The seropositivity among students (25%) was higher than the school staff in September. In a general population survey in October 2009, seropositivity was higher in children (9.1%) than adults (4.3%). The 15-19 years age group showed the highest seropositivity of 20.3%. Seropositivity of seasonal H3N2 (55.3%) and H1N1 (26.4%) was higher than pandemic H1N1 (5.7%) (n = 2328). In households of 74 PCR-confirmed pandemic H1N1 cases, 25.6% contacts were seropositive. Almost 90% pandemic H1N1 infections were asymptomatic or mild. Considering a titre cut off of 1:10, seropositivity was 1.5-3 times as compared to 1:40.

Conclusions

Pandemic influenza A (H1N1) 2009 virus infection was widespread in all sections of community. However, infection was significantly higher in school children and general practitioners. Hospital staff had the lowest infections suggesting the efficacy of infection-control measures.
Computational simulation of vasopressin secretion using a rat model of the water and electrolyte homeostasis
Authors: Nadeau Louis , Arbour Danielle , Mouginot Didier
Published: August 2010

Background

In mammals, vasopressin (AVP) is released from magnocellular neurons of the hypothalamus when osmotic pressure exceeds a fixed set-point. AVP participates to the hydromineral homeostasis (HH) by controlling water excretion at the level of the kidneys. Our current understanding of the HH and AVP secretion is the result of a vast amount of data collected over the five past decades. This experimental data was collected using a number of systems under different conditions, giving a fragmented view of the components involved in HH.

Results

Here, we present a high-level model of the rat HH based on selected published results to predict short-term (hours) to long-term (days) variation of six major homeostatic parameters: (1) the extracellular sodium concentration, (2) the AVP concentration, (3) the intracellular volume, (4) the extracellular volume, (5) the urine volume and (6) the water intake. The simulation generates quantitative predictions like the daily mean of the extracellular sodium concentration (142.2 mmol/L), the AVP concentration, (1.7 pg/ml), the intracellular volume (45.3 ml/100 g body weight - bw), the extracellular volume (22.6 ml/100 g bw), the urine volume (11.8 ml/100 g bw) and the cumulative water intake (18 ml/100 g bw). The simulation also computes the dynamics of all these parameters with a high temporal resolution of one minute. This high resolution predicts the circadian fluctuation of the AVP secretion (5 ± 2 pg/ml) and defines the limits of a restoration and a maintenance phase in the HH (2.1 pg/ml). Moreover, the simulation can predict the action of pharmacological compounds that disrupt the HH. As an example, we tested the action of a diuretic (furosemide) combined with a sodium deficient diet to generate quantitative prediction on the extracellular sodium concentration (134 mmol/L) and the need-induced water intake (20.3 ml/100 g bw). These simulated data are compatible with experimental data (136 ± 3 mmol/L and 17.5 ± 3.5 ml/100 g bw, respectively).

Conclusion

The quantitative agreement of the predictions with published experimental data indicates that our simplified model of the HH integrates most of the essential systems to predict realistic physiological values and dynamics under a set of normal and perturbed hydromineral conditions.