bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived and Capitalization Support Are Substantially Similar: Implications for Social Support Theory
Authors: Shorey Ryan C. , Lakey Brian
Published: April 2011

Social support is typically thought to protect people from bad events, whereas capitalization support augments people’s reactions to good events. Because social support and capitalization support apply to different classes of events, most theory predicts that measures of perceived support and capitalization support should be empirically distinct. We tested a new theory that hypothesizes that the main effects between perceived support and mental health do not reflect stress and coping primarily, but instead reflect ordinary, yet affectively consequential conversations and shared activities, some of which include positive events. According to this view, perceived support and capitalization support should be substantially correlated, should have similar links to other constructs, and their links to favorable affect should overlap, yet not be completely redundant. In three samples, results were consistent with the new theory, when correlations reflected social influences. When correlations reflected trait influences, perceived and capitalization support showed greater overlap.
A Pilot Study of the Effects of Gonadotropin-Releasing Hormone Agonist Therapy on Brain Activation Pattern in a Man With Pedophilia
Authors: Moulier Virginie , Fonteille Véronique , Pélégrini-Issac Mélanie , Cordier Bernard , Baron-Laforêt Sophie , Boriasse Emeline , Durand Emmanuel , Stoléru Serge
Published: April 2011

Gonadotropin-releasing hormone (GnRH) agonists, such as leuprorelin, are recommended in the patients with pedophilia at highest risk of offending. However, the cerebral mechanisms of the effects of these testosterone-decreasing drugs are poorly known. This study aimed to identify changes caused by leuprorelin in a pedophilic patient’s brain responses to pictures representing children. Clinical, endocrine, and fMRI investigations were done of a man with pedophilia before leuprorelin therapy and 5 months into leuprorelin therapy. Patient was compared with an age-matched healthy control also assessed 5 months apart. Before therapy, pictures of boys elicited activation in the left calcarine fissure, left insula, anterior cingulate cortex, and left cerebellar vermis. Five months into therapy, all the above-mentioned activations had disappeared. No such activations and, consequently, no such decreases occurred in the healthy control. The results of this pilot study suggest that leuprorelin decreased activity in regions known to mediate the perceptual, motivational, and affective responses to visual sexual stimuli.
Implications for the Prevention of Aggressive Behavior Within Psychiatric Hospitals Drawn From Interpersonal Communication Theory
Authors: Daffern Michael , Day Andrew , Cookson Amy
Published: April 2011

Although interpersonal style is a defining feature of personality and personality disorder and is commonly identified as an important influence on aggressive behavior, treatment completion, and the development of an effective therapeutic alliance, it is rarely considered in practice guidelines for preventing, engaging, and managing patients at risk of aggression. In this article, the authors consider three potential applications of interpersonal theory to the care and management of patients at risk of aggression during hospitalization: (a) preventing aggression through theoretically grounded limit setting and de-escalation techniques, (b) developing and using interventions to alter problematic interpersonal styles, and (c) understanding therapeutic ruptures and difficulties establishing a therapeutic alliance. Interpersonal theory is proposed to offer a unifying framework that may assist development of intervention and management strategies that can help to reduce the occurrence of aggression in institutional settings.
Differential Outcomes of Court-Supervised Substance Abuse Treatment Among California Parolees and Probationers
Authors: Evans Elizabeth , Jaffe Adi , Urada Darren , Anglin M. Douglas
Published: April 2011

To explore the effectiveness of court-supervised drug treatment for California parolees, offender characteristics, treatment experiences, and outcomes were examined and contrasted to those of probationers. The analysis used statewide administrative data on 4,507 parolees and 22,701 probationers referred to treatment by Proposition 36 during fiscal year 2006-2007. Compared with probationers, parolee problems were more severe at treatment entry, more were treated in residential settings, treatment retention was shorter, and fewer completed treatment. Regarding outcomes, fewer parolees were successful at treatment discharge and more recidivated over 12-months post admission. Both groups improved in many areas by treatment discharge, but improvements were generally smaller among parolees. Significant interaction effects indicated that parolees benefited from residential care and more treatment days, even after controlling for covariates. Court-supervised drug treatment for parolees can “work;” however, parolees have more frequent and diverse needs, and their outcomes are enhanced by more intensive treatment. Findings suggest methods for optimizing the effectiveness of criminal-justice–supervised programs for treating drug-dependent offenders.
Why the Pirate Party Won the German Election of 2009 or The Trouble With Predictions: A Response to Tumasjan, A., Sprenger, T. O., Sander, P. G., & Welpe, I. M. “Predicting Elections With Twitter: What 140 Characters Reveal About Political Sentiment”
Authors: Jungherr Andreas , Jürgens Pascal , Schoen Harald
Published: April 2011

In their article “Predicting Elections with Twitter: What 140 Characters Reveal About Political Sentiment,” the authors Andranik Tumasjan, Timm O. Sprenger, Philipp G. Sandner, and Isabell M. Welpe (TSSW) the authors claim that it would be possible to predict election outcomes in Germany by examining the relative frequency of the mentions of political parties in Twitter messages posted during the election campaign. In this response we show that the results of TSSW are contingent on arbitrary choices of the authors. We demonstrate that as of yet the relative frequency of mentions of German political parties in Twitter message allows no prediction of election results.
The Ties That Bind
Authors: Smith Buster G. , Scheitle Christopher P. , Bader Christopher D.
Published: April 2011

While the availability of Internet data on religious organizations has increased exponentially the use of such resources remains limited. The authors make use of a new research method involving weblink analysis to study nondenominational churches which are difficult to examine using conventional research techniques. One reason for this is the perception that independent churches lack the coherency of denominational populations, which creates methodological and theoretical challenges. The authors explore this assumption by examining the social and symbolic networks of a sample of independent congregations. Using the outgoing links from congregational websites, the authors find that there is more overlap than one might expect. This simultaneously enhances our understanding of this particular religious group as well as demonstrating the usefulness of such a research methodology.
Examining the Dimensions of Hospital Safety Climate and Psychosocial Risk Factors Among Japanese Nurses
Authors: Smith Derek R. , Muto Takashi , Sairenchi Toshimi , Ishikawa Yumiko , Sayama Shizue , Yoshida Atsushi , Townley-Jones Maureen
Published: April 2011

Purpose: The purpose of this study was to examine the dimensions, reliability, and main loading factors associated with a Japanese safety climate and psychosocial risk factor scale. Design: The authors used a cross-sectional survey of nurses from a university teaching hospital in Japan during 2008 ( N = 996). The survey tools were based on components previously identified in a variety of international studies, including the Hospital Safety Climate Scale (HSCS) originally developed by Gershon et al. in 2000. Results: Factor analysis of the Japanese HSCS demonstrated key themes in the areas of workplace-related issues, protective devices or mechanisms, and managerial dimensions (Cronbach’s α = .887). Factor analysis of the psychosocial scale revealed key themes comprising individually related items and group dynamics (Cronbach’s α = .882). Conclusions: This study revealed high internal consistency in the Japanese-language safety climate and psychosocial risk factor scales. The authors also identified various factors and themes consistent with previous international research. Implications for Practice: Transcultural research using standard psychosocial tools can reveal important and reliable findings if carefully translated and adapted for the host environment.
Development of a Spanish HIV/AIDS Symptom Management Guidebook
Authors: Román Elizabeth , Chou Fang-yu
Published: April 2011

Purpose: To provide culturally appropriate HIV/AIDS patient care, it is important to develop symptom management patient education materials for patients with different cultural backgrounds. The purpose of this study was to develop a Spanish version of the Symptom Management Guidebook: Strategies for People Living with HIV/AIDS guidelines and verify its content, perceived feasibility, and usefulness with HIV/AIDS care providers and people living with HIV/AIDS in Puerto Rico. Design: The Symptom Management Guidebook includes self-care strategies to manage 14 common HIV-related symptoms. The Spanish version was developed by adopting and translating through forward and backward translation methods. Seven HIV/AIDS health care providers from San Juan, Puerto Rico, were invited to review and revise the contents. Ten people living with HIV/AIDS from a community AIDS clinic in San Juan participated in a focus group to review the guidebook and discussed its usefulness and feasibility for managing their symptoms. Findings/Results: Participants expressed positive responses and considered an educational guidebook as a helpful tool for self-managing their symptoms. Discussion/Conclusions:: Results suggested that this guidebook may be useful as an intervention strategy for symptom management in HIV/AIDS patients. Implications: Future research can include testing self-managing intervention and its outcomes in culturally diverse HIV/AIDS patients.
“Being Conditioned, yet Becoming Strong”
Authors: Im Eun-Ok , Lee Seung Hee , Chee Wonshik
Published: April 2011

Purpose: This study aimed to explore the menopausal symptom experiences of Asian American midlife women within the contexts of their daily lives using a feminist approach. Design: This was a qualitative online forum study among 13 Asian American women recruited through the Internet. Seven discussion topics related to the menopausal symptom experience were used, and the data were analyzed using thematic analysis. Findings: Five themes emerged: (a) “being conditioned,” (b) “becoming strong,” (c) “appreciating,” (d) “without making a fuss,” and (e) “quiet support.” Discussion, Conclusion, and Implications for Practice: These themes represent the women’s marginalized but empowered experience during menopausal transition.
A 4-Year Integrated Curriculum in Palliative Care for Medical Undergraduates
Authors: Radwany Steven M. , Stovsky Erica J. , Frate Dean M. , Dieter Kevin , Friebert Sarah , Palmisano Barbara , Sanders Margaret
Published: April 2011

In order to graduate physicians prepared to effectively address clinical issues in palliative medicine and to comply with LCME requirements, the Northeastern Ohio Universities Colleges of Medicine and Pharmacy (NEOUCOM) integrated a coordinated four-year palliative care (PC) curriculum. This report describes the development of the longitudinal curriculum and provides helpful resources and strategies to guide clinicians and administrators undertaking similar efforts. This is a retrospective, descriptive report based on data collected throughout development of the new curriculum. A Palliative Care Advisory Committee initiated development of curricula in PC. An Office of Palliative Care was established to assess and coordinate offerings. Curriculum transformation was based on best practices. Two cornerstone pieces are highlighted: a mandatory hospice experience and a case based small group discussion prior to graduation.
Cerebral Asymmetry in Schizophrenia
Authors: Oertel-Knöchel Viola , Linden David E. J.
Published: April 2011

The hemispheres of the human brain are anatomically and functionally asymmetric, and many cognitive and motor functions such as language and handedness are lateralized. This review examines anatomical, psychological, and physiological approaches to the understanding of separate hemispheric functions and their integration. The concept of hemispheric laterality plays a central role in current neuropsychological and pathophysiological models of schizophrenia. Reduced hemispheric asymmetry has also been reported for other mental disorders, for example, bipolar disorder. Recent research reflects an increasing interest in the molecular and population genetics of laterality and its potential link with animal models of schizophrenia. The authors review the principles of laterality and brain asymmetry and discuss the evidence for changes in asymmetry in schizophrenia and other mental disorders.
Matching Mitochondria to Metabolic Needs at Nodes of Ranvier
Authors: Chiu Shing Y.
Published: April 2011

Myelinated axons conduct nerve impulses at high speed using a unique mode of excitation, referred to as saltatory conduction, which is enabled structurally by the narrowing of the site of action potentials to a tiny gap in the axon called the node of Ranvier. With this structural specialization comes an interesting metabolic matching problem. How do mitochondria find and supply energy to these tiny nodes of Ranvier distributed sparsely along a myelinated axon? Does the intense Na+ influx at the node, which is produced by the highest known sodium channel density in all excitable membranes, help guide where mitochondria stop? Evidence suggests that during excitation in the peripheral nervous system, Na+ influx recruits mitochondria to the node by triggering Ca2+ elevation and activating Na+ pumps. Intriguingly, indirect evidence suggests that in the central nervous system, activity recruits mitochondria to the internode (myelin-covered portion of the axon). Metabolic dysfunction thus might produce spatially distinct lesions in PNS and CNS myelinated fibers. Future dissection of regional variation in mitochondrial biology in myelinated axons using live imaging will likely yield surprises about sites of vulnerability in demyelinating diseases and clues for therapeutic intervention strategy.
Central Pattern Generators of the Mammalian Spinal Cord
Authors: Frigon Alain
Published: April 2011

Neuronal networks within the spinal cord of mammals are responsible for generating various rhythmic movements, such as walking, running, swimming, and scratching. The ability to generate multiple rhythmic movements highlights the complexity and flexibility of the mammalian spinal circuitry. The present review describes features of some rhythmic motor behaviors generated by the mammalian spinal cord and discusses how the spinal circuitry is able to produce different rhythmic movements with their own sets of goals and demands.
Applying the Theory of Planned Behavior to Explore the Relation Between Smoke-Free Air Laws and Quitting Intentions
Authors: Macy Jonathan T. , Middlestadt Susan E. , Seo Dong-Chul , Kolbe Lloyd J. , Jay Stephen J.
Published: April 2011

Smoke-free air policies have been shown to reduce smoking, but the mechanism of behavior change is not well understood. The authors used structural equation modeling to conduct a theory of planned behavior analysis with data from 395 smokers living in seven Texas cities, three with a comprehensive smoke-free air law and four without a comprehensive law. Agreement with regulating smoking in public places was significantly associated with attitudes and perceived normative pressure about quitting. Nicotine dependence was significantly associated with attitudes and perceived behavioral control. There was also a direct effect of nicotine dependence on intention to take measures to quit smoking. Smoke-free air laws appear to influence quitting intentions through the formation of positive attitudes about regulating smoking in public places and the perception of normative pressure to take measures to quit. Implications for smoke-free air policy campaigns and challenges in evaluating their effectiveness are discussed.
Writing the news: A comparison of objective, religious, and political opinion presses
Authors: Young Abbott Jennifer
Published: April 2011

In 1997 in Washington, DC, the Christian men’s group Promise Keepers organized a large rally that drew attention from mainstream newspapers, religious publications, and political opinion journals. Scholarship of this news coverage has downplayed differences across media and suggested, instead, that nearly all favored Promise Keepers. This study attempts to correct that oversight by contrasting the news stories in The Washington Post, Christianity Today, and several political opinion journals. Based on this analysis, I argue that The Washington Post produced the most positive coverage of Promise Keepers, while Christianity Today published more skeptical reports, and political opinion journals provided the fairest coverage. I suggest the writing practices associated with each type of journalism help to account for the differences in reporting. In the end, this study reveals the impact of journalistic formats on news coverage and reminds us that all news reflects a particular perspective.
The immediacy of online news, the visibility of journalistic processes and a restructuring of journalistic authority
Authors: Karlsson Michael
Published: April 2011

Transparency has been emphasized as a new norm within journalism and has received a great deal of attention. The credo of transparency is openness, and the interactive potential of digital media has been identified as one key element in achieving openness. In this essay it is argued that by exposing previously hidden journalistic processes, the high speed of online news plays a part in this orientation towards transparency in journalism.
Emotion aside or emotional side? Crafting an ‘experience of involvement’ in the news
Authors: Peters Chris
Published: April 2011

In relation to journalism, the concept of ‘emotion’ is consistently undertheorized. Employed with commonsensical discernment, it is conflated with tabloid practices, sensationalism, bias, commercialization, and the like. Consequently, when discussed, emotion is often treated dismissively; a marker of unprincipled and flawed journalism. Yet hard, self-styled objective, ‘just the facts’ journalism is not unemotional, just as soft, so-called tabloid news is not irrational. For authors who study the sociology of emotions note, emotion has a social component and can more broadly be conceptualized as the experience of involvement. This article utilizes this understanding to interrogate traditional news dichotomies before applying this perspective to consider non-valorized news alternatives. One significant change over the past few decades is not that the news has become emotional (indeed, it has always been); rather, the diversity of emotional styles, the acceptability of journalistic involvement, and attempts to involve the audience have become more explicit.
The interaction between experts and journalists in news journalism
Authors: Albæk Erik
Published: April 2011

The article investigates why journalists choose to use experts as sources in their news coverage and the nature of the interaction of experts and journalists. During a month-long period in 2003, both journalists and experts were contacted on the day a news article appearing in one of the three largest national Danish newspapers referred to experts. In the vast majority of the cases, the contact comes as the result of initiatives taken by the journalists (approximately 90% of the cases), not the other way around (1 — 2% of the cases). Relatively active interaction proceeds between experts and journalists, whereby the expert generally provides background knowledge and serves as a sparring partner for the journalist in the attempts of the latter to interpret a given event or course of events on the public agenda.
Expanding the scope of paradigmatic research in journalism studies: The case of early mainstream Israeli journalism and its discontents
Authors: Meyers Oren
Published: April 2011

This article argues that existing scholarship on paradigmatic crises in journalism neglects some of the fundamental dynamics that were explored in Kuhn’s original work. In order to fully conceptualize the creation and alteration of news paradigms, journalism scholars ought to study ‘paradigmatic challenges’: the multifaceted ways by which journalistic communities react to planned, methodical, and continuous challenges that offer comprehensive paradigmatic alternatives to existing core professional convictions. To operationalize this research interest, the article explores a salient case study: the multi-dimensional response of early Israeli mainstream journalism to the paradigmatic challenge posed by the radical and sensational weekly Haolam Hazeh.
Acclimation Effects and the Chief Justice: The Influence of Tenure and Role on the Decisional Behavior of the Court’s Leader, 1888-2007
Authors: Noble Lanier Drew
Published: April 2011

Under the acclimation effect view, recent appointees to the Court modify their behavior in systematic ways early in their tenure as opposed to their later decisional tendencies. Similarly, many studies have examined the chief justice’s unique behavior.This study blends these two rich strands and explores whether chief justices demonstrate an acclimation effect, such that their behavior changes systematically through time. Using more than a century of Court data, this study examines whether new chief justices’ concurrence and dissent rates decline and whether they write fewer individual opinions gradually. I find that the chief justice’s position serves to create an incentive structure that is uniquely associated with declining rates of specially concurring and dissenting votes in certain cases. Also, new chief justices pen fewer special concurrences and dissents in some policy areas. My results hence imply that the chief justice experiences unique acclimation effects in learning to marshal the Court.
Comparing Institutional and Policy Explanations for the Adoption of State Constitutional Amendments
Authors: Hume Robert J.
Published: April 2011

The literature on state constitutional amendments remains undeveloped despite recent activity in the area of same-sex marriage policy. Previous studies have assumed that the adoption of state constitutional amendments is governed by routine policy considerations, but there are strong theoretical reasons for expecting attributes of state institutions also to affect adoption. In this study, I compare institutional and policy explanations for the enactment of state constitutional amendments prohibiting same-sex marriage. Although I expect routine policy considerations to affect the adoption of amendments, I also expect adoption to be influenced by attributes of state institutions, in particular, the capacity of state high courts to produce decisions favoring marriage equality. Using event history analysis, I find that the initial consideration of amendments is driven by policy considerations but that adoption is also guided by institutional considerations, such as the professionalization of state high courts.
Sex and Race Effects on Risk for Selected Outcomes among Elderly HIV-Infected Patients
Authors: Frontini Maria , Chotalia Jigar , Spizale Lauren , Onya Wilfred , Ruiz Marco , Clark Rebecca A.
Published: April 2011

The HIV-infected population in the United States is aging. A retrospective study of 132 patients (26 women, 106 men) ≥59 years of age was undertaken to evaluate the effect of race and sex on selected outcomes. With the exception of women being more likely to have diagnosis of depression compared with men, sex had little influence on risk for other conditions among elderly patients with HIV. In contrast, African American race was significantly associated with the risk for several selected disorders and outcomes. These results can assist in future prevention efforts among senior individuals with HIV infection.
RUNX1 regulates corepressor interactions of PU.1
Authors: Hu Zhenbo , Gu Xiaorong , Baraoidan Kristine , Ibanez Vinzon , Sharma Arun , Kadkol ShriHari , Munker Reinhold , Ackerman Steven , Nucifora Giuseppina , Saunthararajah Yogen
Published: April 2011

The transcription factor (TF) RUNX1 cooperates with lineage-specifying TFs (eg, PU.1/SPI1) to activate myeloid differentiation genes, such as macrophage and granulocyte macrophage colony-stimulating factor receptors (MCSFR and GMCSFR). Disruption of cooperative gene activation could contribute to aberrant repression of differentiation genes and leukemogenesis initiated by mutations and translocations of RUNX1. To investigate the mechanisms underlying cooperative gene activation, the effects of Runx1 deficiency were examined in an in vitro model of Pu.1-driven macrophage differentiation and in primary cells. Runx1 deficiency decreased Pu.1-mediated activation of Mcsfr and Gmcsfr, accompanied by decreased histone acetylation at the Mcsfr and Gmcsfr promoters, and increased endogenous corepressor (Eto2, Sin3A, and Hdac2) coimmunoprecipitation with Pu.1. In cotransfection experiments, corepressors were excluded from a multiprotein complex containing full-length RUNX1 and PU.1. However, corepressors interacted with PU.1 if wild-type RUNX1 was replaced with truncated variants associated with leukemia. Histone deacetylase (HDAC) enzyme activity is a major component of corepressor function. HDAC inhibition using suberoylanilide hydroxamic acid or MS-275 significantly increased MCSFR and GMCSFR expression in leukemia cell lines that express PU.1 and mutated or translocated RUNX1. RUNX1 deficiency is associated with persistent corepressor interaction with PU.1. Thus, inhibiting HDAC can partly compensate for the functional consequences of RUNX1 deficiency.
Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report
Authors: Silver Richard T. , Vandris Katherine , Goldman Joshua J.
Published: April 2011

The limited effects of current treatments of primary myelofibrosis (PM) led us to prospectively evaluate recombinant interferon-α (rIFNα) in “early” PM patients with residual hematopoiesis and only grade 1 or 2 myelofibrosis. Seventeen patients meeting World Health Organization PM diagnostic criteria received either rIFNα-2b 500 000 to 3 million units 3 times weekly, or pegylated rIFNα-2a 45 or 90 μg weekly. International Working Group for Myelofibrosis Research and Treatment criteria for prognosis and response were used. Eleven patients were women and 6 were men. Their median age at diagnosis was 57 years. Eleven patients were low risk and 6 were intermediate-1 risk. Two achieved complete remission, 7 partial, 1 clinical improvement, 4 stable disease, and 3 had progressive disease. Thus, more than 80% derived clinical benefit or stability. Improvement in marrow morphology occurred in 4. Toxicity was acceptable. These results, with documented marrow reversion because of interferon treatment, warrant expanded evaluation.
MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome
Authors: Wang Qian-fei , Wu George , Mi Shuangli , He Fuhong , Wu Jun , Dong Jingfang , Luo Roger T. , Mattison Ryan , Kaberlein Joseph J. , Prabhakar Shyam , Ji Hongkai , Thirman Michael J.
Published: April 2011

MLL encodes a histone methyltransferase that is critical in maintaining gene expression during embryonic development and hematopoiesis. 11q23 translocations result in the formation of chimeric MLL fusion proteins that act as potent drivers of acute leukemia. However, it remains unclear what portion of the leukemic genome is under the direct control of MLL fusions. By comparing patient-derived leukemic cell lines, we find that MLL fusion-bound genes are a small subset of that recognized by wild-type MLL. In an inducible MLL-ENL model, MLL fusion protein binding and changes in H3K79 methylation are limited to a specific portion of the genome, whereas wild-type MLL distributes to a much larger set of gene loci. Surprisingly, among 223 MLL-ENL–bound genes, only 12 demonstrate a significant increase in mRNA expression on induction of the fusion protein. In addition to Hoxa9 and Meis1, this includes Eya1 and Six1, which comprise a heterodimeric transcription factor important in several developmental pathways. We show that Eya1 has the capacity to immortalize hematopoietic progenitor cells in vitro and collaborates with Six1 in hematopoietic transformation assays. Altogether, our data suggest that MLL fusions contribute to the development of acute leukemia through direct activation of a small set of target genes.
SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma
Authors: Casasnovas René-Olivier , Meignan Michel , Berriolo-Riedinger Alina , Bardet Stéphane , Julian Anne , Thieblemont Catherine , Vera Pierre , Bologna Serge , Brière Josette , Jais Jean-Philippe , Haioun Corinne , Coiffier Bertrand , Morschhauser Franck
Published: April 2011

The prognostic value of interim positron emission tomography (PET) interpreted according to visual criteria is a matter of debate in diffuse large B-cell lymphoma (DLBCL). Maximal standardized uptake value reduction (ΔSUVmax) may better predict outcome. To compare the prognostic value of both methods, we analyzed PET done at baseline (PET0) and after 2 (PET2) and 4 (PET4) cycles in 85 patients with high-risk DLBCL enrolled on a prospective multicenter trial. All images were centrally reviewed and interpreted visually according to the International Harmonization Project criteria and by computing ΔSUVmax between PET0 and PET2 (ΔSUVmaxPET0-2) or PET4 (ΔSUVmaxPET0-4). Optimal cutoff to predict progression or death was 66% for ΔSUVmaxPET0-2 and 70% for ΔSUVmaxPET0-4. Outcomes did not differ significantly whether PET2 and PET4 were visually positive or negative. Inversely, ΔSUVmaxPET0-2 analysis (> 66% vs ≤ 66%) identified patients with significantly different 2-year progression-free survival (77% vs 57%; P = .0282) and overall survival (93% vs 60%; P < .0001). ΔSUVmaxPET0-4 analysis (> 70% vs ≤ 70%) seemed even more predictive for 2-year progression-free survival (83 vs 40%; P < .0001) and overall survival (94% vs 50%; P < .0001). ΔSUVmax analysis of sequential interim PET is feasible for high-risk DLBCL and better predicts outcome than visual analysis. The trial was registered at http://clinicaltrials.gov as NCT00498043.
NKG2D receptor regulates human effector T-cell cytokine production
Authors: Barber Amorette , Sentman Charles L.
Published: April 2011

Although innate immune signals shape the activation of naive T cells, it is unclear how innate signals influence effector T-cell function. This study determined the effects of stimulating the NKG2D receptor in conjunction with the TCR on human effector CD8+ T cells. Stimulation of CD8+ T cells through CD3 and NKG2D simultaneously or through a chimeric NKG2D receptor, which consists of NKG2D fused to the intracellular region of CD3ζ, activated β-catenin and increased expression of β-catenin–induced genes, whereas T cells stimulated through the TCR or a combination of the TCR and CD28 did not. Activation by TCR and NKG2D prevented expression and production of anti-inflammatory cytokines IL-10, IL-9, IL-13, and VEGF-α in a β-catenin– and PPARγ- dependent manner. NKG2D stimulation also modulated the cytokine secretion of T cells activated simultaneously through CD3 and CD28. These data indicate that activating CD8+ T cells through the NKG2D receptor along with the TCR modulates signal transduction and the production of anti-inflammatory cytokines. Thus, human effector T cells alter their function depending on which innate receptors are engaged in conjunction with the TCR complex.
Individual patient data meta-analysis of randomized trials evaluating IL-2 monotherapy as remission maintenance therapy in acute myeloid leukemia
Authors: Buyse Marc , Squifflet Pierre , Lange Beverly J. , Alonzo Todd A. , Larson Richard A. , Kolitz Jonathan E. , George Stephen L. , Bloomfield Clara D. , Castaigne Sylvie , Chevret Sylvie , Blaise Didier , Maraninchi Dominique , Lucchesi Kathryn J. , Burzykowski Tomasz
Published: April 2011

IL-2 is a natural, T cell–derived cytokine that stimulates the cytotoxic functions of T and natural killer cells. IL-2 monotherapy has been evaluated in several randomized clinical trials (RCTs) for remission maintenance in patients with acute myeloid leukemia (AML) in first complete remission (CR1), and none demonstrated a significant benefit of IL-2 monotherapy. The objective of this meta-analysis was to reliably determine IL-2 efficacy by combining all available individual patient data (IPD) from 5 RCTs (N = 905) and summary data from a sixth RCT (N = 550). Hazard ratios (HRs) were estimated using Cox regression models stratified by trial, with HR < 1 indicating treatment benefit. Combined IPD showed no benefit of IL-2 over no treatment in terms of leukemia-free survival (HR = 0.97; P = .74) or overall survival (HR = 1.08; P = .39). Analyses including the sixth RCT yielded qualitatively identical results (leukemia-free survival HR = 0.96, P = .52; overall survival HR = 1.06; P = .46). No significant heterogeneity was found between the trials. Prespecified subset analyses showed no interaction between the lack of IL-2 effect and any factor, including age, sex, baseline performance status, karyotype, AML subtype, and time from achievement of CR1 to initiation of maintenance therapy. We conclude that IL-2 alone is not an effective remission maintenance therapy for AML patients in CR1.
Pulmonary arterial dysfunction in insulin resistant obese Zucker rats
Authors: Moral-Sanz Javier , Menendez Carmen , Moreno Laura , Moreno Enrique , Cogolludo Angel , Perez-Vizcaino Francisco
Published: April 2011

Background

Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat.

Methods

Large and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. KV currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique.

Results

Right ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, KV1.5 and 5-HT2A receptor mRNA and protein expression and KV current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance) pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT) was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.

Conclusions

In contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.
Recent acquisition of imprinting at the rodent Sfmbt2 locus correlates with insertion of a large block of miRNAs
Authors: Wang Qianwei , Chow Jacqueline , Hong Jenny , Smith Anne Ferguson , Moreno Carol , Seaby Peter , Vrana Paul , Miri Kamelia , Tak Joon , Chung Eu Ddeum , Mastromonaco Gabriela , Caniggia Isabella , Varmuza Susannah
Published: April 2011

Background

The proximal region of murine Chr 2 has long been known to harbour one or more imprinted genes from classic genetic studies involving reciprocal translocations. No imprinted gene had been identified from this region until our study demonstrated that the PcG gene Sfmbt2 is expressed from the paternally inherited allele in early embryos and extraembryonic tissues. Imprinted genes generally reside in clusters near elements termed Imprinting Control Regions (ICRs), suggesting that Sfmbt2 might represent an anchor for a new imprinted domain.

Results

We analyzed allelic expression of approximately 20 genes within a 3.9 Mb domain and found that Sfmbt2 and an overlapping non-coding antisense transcript are the only imprinted genes in this region. These transcripts represent a very narrow imprinted gene locus. We also demonstrate that rat Sfmbt2 is imprinted in extraembryonic tissues. An interesting feature of both mouse and rat Sfmbt2 genes is the presence of a large block of miRNAs in intron 10. Other mammals, including the bovine, lack this block of miRNAs. Consistent with this association, we show that human and bovine Sfmbt2 are biallelic. Other evidence indicates that pig Sfmbt2 is also not imprinted. Further strengthening the argument for recent evolution of Sfmbt2 is our demonstration that a more distant muroid rodent, Peromyscus also lacks imprinting and the block of miRNAs.

Conclusions

These observations are consistent with the hypothesis that the block of miRNAs are driving imprinting at this locus. Our results are discussed in the context of ncRNAs at other imprinted loci.

Accession numbers for Peromyscus cDNA and intron 10 genomic DNA are [Genbank:HQ416417 and Genbank:HQ416418], respectively.
Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur
Authors: Berrêdo-Pinho Marcia , Kalume Dario E , Correa Paloma R , Gomes Leonardo HF , Pereira Melissa P , da Silva Renata F , Castello-Branco Luiz RR , Degrave Wim M , Mendonça-Lima Leila
Published: April 2011

Background

Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB) and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO) affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE) and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs) from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection.

Results

The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa), Rv1926c (BCG1965c, Mpb63) and Rv1886c (BCG1923c, Ag85B) in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2) and Rv0350 (BCG0389, DnaK), show the opposite pattern.

Conclusions

Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.
Isolation and characterization of Ehrlichia chaffeensis RNA polymerase and its use in evaluating p28 outer membrane protein gene promoters
Authors: Faburay Bonto , Liu Huitao , Peddireddi Lalitha , Ganta Roman R
Published: April 2011

Background

Ehrlichia chaffeensisis a tick-transmitted rickettsial pathogen responsible for an important emerging disease, human monocytic ehrlichiosis. To date howE. chaffeensis and many related tick-borne rickettsial pathogens adapt and persist in vertebrate and tick hosts remain largely unknown. In recent studies, we demonstrated significant host-specific differences in protein expression inE. chaffeensisoriginating from its tick and vertebrate host cells. The adaptive response of the pathogen to different host environments entails switch of gene expression regulated at the level of transcription, possibly by altering RNA polymerase activity.

Results

In an effort to understand the molecular basis of pathogen gene expression differences, we isolated nativeE. chaffeensisRNA polymerase using a heparin-agarose purification method and developed anin vitrotranscription system to map promoter regions of two differentially expressed genes of the p28 outer membrane protein locus,p28-Omp14andp28-Omp19. We also prepared a recombinant protein ofE. chaffeensisσ70 homologue and used it forin vitropromoter analysis studies. The possible role of one or more proteins presents inE. chaffeensislysates in binding to the promoter segments and on the modulation ofin vitrotranscription was also assessed.

Conclusions

Our experiments demonstrated that both the native and recombinant proteins are functional and have similar enzyme properties in driving the transcription fromE. chaffeensispromoters. This is the first report of the functional characterization ofE. chaffeensisRNA polymerase andin vitromapping of the pathogen promoters using the enzyme. This study marks the beginning to broadly characterize the mechanisms controlling the transcription byAnaplasmataceaepathogens.
RecA Proteins from Deinococcus geothermalis and Deinococcus murrayi - Cloning, Purification and Biochemical Characterisation
Authors: Wanarska Marta , Krawczyk Beata , Hildebrandt Piotr , Kur Józef
Published: April 2011

Background

Escherichia coli RecA plays a crucial role in recombinational processes, the induction of SOS responses and mutagenic lesion bypasses. It has also been demonstrated that RecA protein is indispensable when it comes to the reassembly of shattered chromosomes in γ-irradiated Deinococcus radiodurans, one of the most radiation-resistant organisms known. Moreover, some functional differences between E. coli and D. radiodurans RecA proteins have also been shown.

Results

In this study, recA genes from Deinococcus geothermalis and Deinococcus murrayi, bacteria that are slightly thermophilic and extremely γ-radiation resistant, were isolated, cloned and expressed in E. coli. After production and purification, the biochemical properties of Dge RecA and Dmu RecA proteins were determined. Both proteins continued to exist in the solutions as heterogenous populations of oligomeric forms. The DNA binding by Dge RecA and Dmu RecA proteins is stimulated by Mg2+ ions. Furthermore, both proteins bind more readily to ssDNA when ssDNA and dsDNA are in the same reaction mixture. Both proteins are slightly thermostable and were completely inactivated in 10 s at 80°C. Both proteins hydrolyze ATP and dATP in the presence of ssDNA or complementary ssDNA and dsDNA, but not in the absence of DNA or in the presence of dsDNA only, and dATP was hydrolyzed more rapidly than ATP. They were also able to promote DNA strand exchange reactions by a pathway common for other RecA proteins. However, we did not obtain DNA strand exchange products when reactions were performed on an inverse pathway, characteristic for RecA of D. radiodurans.

Conclusions

The characterization of Dge RecA and Dmu RecA proteins made in this study indicates that the unique properties of D. radiodurans RecA are probably not common among RecA proteins from Deinococcus sp.
Novel reference genes for quantifying transcriptional responses of Escherichia coli to protein overexpression by quantitative PCR
Authors: Zhou Kang , Zhou Lihan , Lim Qing 'En , Zou Ruiyang , Stephanopoulos Gregory , Too Heng-Phon
Published: April 2011

Background

Accurate interpretation of quantitative PCR (qPCR) data requires normalization using constitutively expressed reference genes. Ribosomal RNA is often used as a reference gene for transcriptional studies in E. coli. However, the choice of reliable reference genes has not been systematically validated. The objective of this study is to identify a set of reliable reference genes for transcription analysis in recombinant protein over-expression studies in E. coli.

Results

In this study, the meta-analysis of 240 sets of single-channel Affymetrix microarray data representing over-expressions of 63 distinct recombinant proteins in various E. coli strains identified twenty candidate reference genes that were stably expressed across all conditions. The expression of these twenty genes and two commonly used reference genes, rrsA encoding ribosomal RNA 16S and ihfB, was quantified by qPCR in E. coli cells over-expressing four genes of the 1-Deoxy-D-Xylulose 5-Phosphate pathway. From these results, two independent statistical algorithms identified three novel reference genes cysG, hcaT, and idnT but not rrsA and ihfB as highly invariant in two E. coli strains, across different growth temperatures and induction conditions. Transcriptomic data normalized by the geometric average of these three genes demonstrated that genes of the lycopene synthetic pathway maintained steady expression upon enzyme overexpression. In contrast, the use of rrsA or ihfB as reference genes led to the mis-interpretation that lycopene pathway genes were regulated during enzyme over-expression.

Conclusion

This study identified cysG/hcaT/idnT to be reliable novel reference genes for transcription analysis in recombinant protein producing E. coli.