bluuebunny/crossref_metadata_2025 huggingface dataset:
Cybersexuality in MMORPGs: Virtual Sexual Revolution Untapped
Authors: Cypress Valkyrie Zek
Published: May 2010

This study explores the mechanics and perceptions of cybersex interactions in massively multiplayer online role playing games (MMORPGs) and examines the potential for cybersex in gaming to revolutionize sexuality politics. Drawing on ethnographic and in-depth interview data with fifty MMORPG players, the author examines how cybersex interactions are performed, the context in which they are allowed, and the assessments players make about the utility of cybersex. The author suggests that cybersex has yet to embrace a broader spectrum of sexuality even in strictly virtual interactions.
Earn Yo’ Respect! Respect in the Status Struggle of Finnish School Boys
Authors: Manninen Sari , Huuki Tuija , Sunnari Vappu
Published: May 2010

What is respect among school boys and how can it be earned? Reaching across disciplines, this article contends that respect is a dimension of status in the context of masculinities in peer relations, as are peer likeability and power positions. Drawing on longitudinal interviews and observational material, the authors scrutinize violence, physicality, materiality, and performances, exploring how school boys use these resources strategically to gain respect and to affect power relations. The authors conceptualize respect further, suggesting that respect among school boys refers not only to peer likeability but to a self-oriented stance tied to power and masculine veneration. This research aims to dig deeply into the complexities of masculinities, status, and power; to openly subvert, change, and make room for ‘‘fair power’’ instead of ‘‘fear power’’ in schools.
The Effects of Hydrotherapy on Anxiety, Pain, Neuroendocrine Responses, and Contraction Dynamics During Labor
Authors: Benfield Rebecca D. , Hortobágyi Tibor , Tanner Charles J. , Swanson Melvin , Heitkemper Margaret M. , Newton Edward R.
Published: May 2010

Background: Hydrotherapy (immersion or bathing) is used worldwide to promote relaxation and decrease parturient anxiety and pain in labor, but the psychophysiological effects of this intervention remain obscure. Design: A pretest—posttest design with repeated measures was used to examine the effects of hydrotherapy on maternal anxiety and pain, neuroendocrine responses, plasma volume shift (PVS), and uterine contractions (CXs) during labor. Correlations among variables were examined at three time points (preimmersion and twice during hydrotherapy). Methods: Eleven term women (mean age 24.5 years) in spontaneous labor were immersed to the xiphoid in 37 °C water for 1 hr. Blood samples and measures of anxiety and pain were obtained under dry baseline conditions and repeated at 15 and 45 min of hydrotherapy. Uterine contractions were monitored telemetrically. Results: Hydrotherapy was associated with decreases in anxiety, vasopressin (V), and oxytocin (O) levels at 15 and 45 min (all ps < .05). There were no significant differences between preimmersion and immersion pain or cortisol (C) levels. Pain decreased more for women with high baseline pain than for women with low baseline levels at 15 and 45 min. Cortisol levels decreased twice as much at 15 min of hydrotherapy for women with high baseline pain as for those with low baseline pain. β-endorphin (βE) levels increased at 15 min but did not differ between baseline and 45 min. During immersion, CX frequency decreased. A positive PVS at 15 min was correlated with contraction duration. Conclusions: Hydrotherapy during labor affects neuroendocrine responses that modify psychophysiological processes.
The Heritability of Postpartum Depression
Authors: Corwin Elizabeth J. , Kohen Ruth , Jarrett Monica , Stafford Brian
Published: May 2010

Postpartum depression (PPD) is a serious mood disorder that may carry life-long consequences for a woman and her family. Multiple risk factors for PPD have been identified, including psychosocial, situational, and biological stimuli, several of which are experienced by most, if not all, postpartum women. Given the commonality of these risk factors, it is unclear why fewer than 20% of postpartum women actually develop PPD. In this review, we suggest that different susceptibility to PPD among postpartum women may be explained by the presence or absence of genetic variants that confer increased risk. We review three categories of genes known to code for proteins associated with depression in the general population or proteins known to be affected by childbirth for their possible association with PPD, including genes related to central nervous system monoamine availability, proinflammatory cytokines, and brain neuropeptides. Only two studies are available in the literature to date specifically looking at polymorphisms in postpartum women as related to PPD; both are concerned with monoamine availability. These are discussed in further depth. Conclusions regarding the contribution of genetic polymorphisms to the development of PPD are mixed. Ultimately, the complexity of the disorder and the interrelationships among different genes thought to contribute to depression suggest that much more research is required to understand the heritability of PPD. The complexity of the disorder also suggests that epigenetic influences must be considered as well when discussing susceptibility.
Discursive Dynamics in Gender Equality Politics
Authors: Lombardo Emanuela , Meier Petra , Verloo Mieke
Published: May 2010

Discursive dynamics play an important role in shaping the meanings of gender equality. The article discusses the relation between hegemonic discourses on gender equality policies and feminist taboos. It suggests that feminist scholars could paradoxically be trapped in hegemonic discourses on gender equality policies that may lead to taboos about particular approaches to and interpretations of such policies. Three main feminist hegemonic discourses are considered to act as taboos. They deal with the possibility to overcome patriarchy, the role of elites and other groups of actors in processes of gender transformation and the merits of incremental change. The article further discusses the implications of the postulate about hegemonic discourses and taboos on gender equality for feminist knowledge production and reflects on the potential of Bacchi’s notion of ‘reflexivity’ to overcome them.
Community and consent
Authors: Svensson Isak , Lindgren Mathilda
Published: May 2010

This study explores popular challenges against the state through nonviolent means. Although previous research has started to examine the effect of these ‘unarmed insurrections’, the relationship between challenging the state apparatus (vertical legitimacy) and the state identity (horizontal legitimacy) has not been adequately addressed. We argue that unarmed insurrections are most likely to be successful when challenging the vertical, rather than the horizontal, legitimacy of the state. Studying data for 287 years of protests in 57 non-democratic countries during the period of 1946–2006, we find support for three implications of this proposition: 1) campaigns that demand governmental regime change are more successful than campaigns for territorial changes; 2) success is less likely when the identity of the insurgents and the government is split along ethnic lines; and 3) success is less likely when society is highly polarized along ethnic lines rather than being ethnically homogeneous. Thus, when the community is divided, the efforts to withdraw consent will be less effective. The study discusses the implications of these findings for policymakers and scholars interested in nonviolent strategic action.
Processes Associated with Participation and Adherence to a 12-month Exercise Programme for Adults Aged 70 and older
Authors: Stathi A. , Mckenna J. , Fox K.R.
Published: May 2010

This study investigated the processes associated with the engagement of adults aged 70 years and older in a 12-month long research-based structured exercise programme. A sample of 21 participants (Mean age (SD) 75.8 (3.9); 14 females) and six exercise class leaders or researchers involved in the programme participated in individual semi-structured interviews. Transcripts were analysed with the principles of interpretive qualitative analysis. Our findings suggest that a programme that runs locally, provides individual attention/tailoring, delivers meaningful benefits, offers a staged approach to efficacy building, creates a sense of ownership, and provides intergenerational support and opportunities for social interaction, facilitates exercise engagement in later life.
Indoor Tanning, Mental Health, and Substance Use among College Students
Authors: Mosher Catherine E. , Danoff-Burg Sharon
Published: May 2010

This study examined relations among indoor tanning frequency, symptoms of depression, anxiety, and obsessive-compulsive disorder, and substance use. A total of 421 college students (68% female) completed self-report measures on one occasion. Among men, indoor tanning was positively associated with symptoms of anxiety and obsessive-compulsive disorder, whereas indoor tanning was unrelated to these symptoms among women. Among women, indoor tanning was positively associated with the use of alcohol, tobacco, and other substances. Further research is needed to explore contextual and coping processes that may underlie these gender differences.
Cognitive Coping, Goal Adjustment, and Depressive and Anxiety Symptoms in People Undergoing Infertility Treatment
Authors: Kraaij Vivian , Garnefski Nadia , Schroevers Maya J. , Weijmer Janneke , Helmerhorst Frans
Published: May 2010

The relationships between cognitive coping strategies, goal adjustment, and symptoms of depression and anxiety were studied in people with fertility problems. Both cross-sectional and prospective relationships were studied in a sample of 313 patients attending an infertility clinic. Self-report questionnaires were filled out at home. Positive refocusing, rumination and catastrophizing, and goal reengagement were related to symptoms of depression and anxiety. When looking at the long-term effects, rumination and catastrophizing were also related to emotional problems nine months later. These findings suggest that intervention programs should focus on cognitive coping strategies and goal-based processes.
Cancer Ward
Authors: Kaptein Ad A. , Lyons Antonia C.
Published: May 2010

The novel Cancer ward (Solzhenitsyn, 1968) was used to examine the perceptions that cancer patients hold regarding their illness and its treatment, and how these perceptions relate to theoretical models in health psychology. Excerpts were identified, categorized and interpreted using the Self-Regulation Model of illness. The model’s dimensions of illness perceptions were apparent throughout Cancer ward. Patients held specific representations about cancer, many of which are similar to those found today. Analysing a novel on cancer provides insight into patients’ embodied experiences and perceptions of cancer and treatment. Incorporating illness perceptions into medical care improves the quality of life of patients.
Approach and Avoidance Coping and Regulatory Focus in Patients Having Coronary Artery Bypass Graft Surgery
Authors: Bergvik Svein , Sørlie Tore , Wynn Rolf
Published: May 2010

Coronary artery bypass graft (CABG) surgery is stressful, and the patient’s coping affects recovery and outcome. The aim of the study was to identify patients’ thoughts and concerns, and explore the relevance of approach/avoidant coping and Regulatory Focus Theory (RFT). Nine patients were interviewed, using an interpretative phenomenological approach. The patients made use of various avoidant (e.g. neglecting symptoms, delaying help-seeking, avoiding thoughts) and approach strategies (e.g. persistent search for the diagnosis, mental preparation for surgery). RFT versus approach/avoidant coping is discussed. RFT may contribute to our understanding of motivational cognitions in patients’ coping with illness and treatment.
Health Risk Behaviors among College Youths
Authors: Khallad Yacoub
Published: May 2010

The present study examined the frequency of smoking, seatbelt use, and vehicular speeding among American and Jordanian college students, and assessed the relationship between these risk behaviors and gender, socioeconomic status, and religiosity. Significantly more Jordanian students were smokers. Jordanian students were less likely than American students to buckle up, but American students were more likely to engage in vehicular speeding. Female students, especially among Jordanians, were less likely than male students to engage in risky behaviors. Among Jordanian participants, smoking and passenger seatbelt use were positively associated with indices of socioeconomic status, and smoking was negatively associated with religiosity.
Changes in Intentions, Planning, and Self-efficacy Predict Changes in Behaviors
Authors: Reuter Tabea , Ziegelmann Jochen P. , Wiedemann Amelie U. , Geiser Christian , Lippke Sonia , Schüz Benjamin , Schwarzer Ralf
Published: May 2010

Can latent true changes in intention, planning, and self-efficacy account for latent change in two health behaviors (physical activity as well as fruit and vegetable intake)? Baseline data on predictors and behaviors and corresponding follow-up data four weeks later were collected from 853 participants. Interindividual differences in change and change—change associations were analyzed using structural equation modeling. For both behaviors, similar prediction patterns were found: changes in intention and self-efficacy predicted changes in planning, which in turn corresponded to changes in behavior. This evidence confirms that change predicts change, which is an inherent precondition in behavior change theories.
Job Satisfaction, Life Satisfaction and Burnout in French Anaesthetists
Authors: Chiron Bruno , Michinov Estelle , Olivier-Chiron Elodie , Laffon Marc , Rusch Emmanuel
Published: May 2010

The present study aimed to examine the prevalence of burnout, levels of life satisfaction and job satisfaction in anaesthetists in France. A cross-sectional study was conducted among 193 anaesthetists from eight French public hospitals. The results indicated low levels of emotional exhaustion and depersonalization scores, but high levels of reduced accomplishment. The results also revealed differences between subgroups: physician anaesthetists reported higher levels of depersonalization and reduced accomplishment than nurse anaesthetists, female and junior anaesthetists reported higher levels of emotional exhaustion and job dissatisfaction than male and senior anaesthetists. The results and the implications to reduce burnout symptoms in anesthesia teams are discussed.
An Information-Motivation-Behavioral Skills Analysis of Diet and Exercise Behavior in Puerto Ricans with Diabetes
Authors: Osborn Chandra Y. , Rivet Amico K. , Fisher William A. , Egede Leonard E. , Fisher Jeffrey D.
Published: May 2010

Frameworks are needed to inform diabetes self-care programs for diverse populations. We tested the Information—Motivation—Behavioral Skills (IMB) model in a sample of Puerto Ricans with Type 2 diabetes ( N = 118). Structural equation models evaluated model fit and interrelations between IMB constructs. For diet behavior, information and motivation related to behavioral skills ( r = 0.19, p < .05 and r = 0.39, p < .01, respectively); behavioral skills related to behavior ( r = 0.42, p < .01 and r = 0.32, p < .05); and behavior related to glycemic control ( r = —0.26, p < .05). For exercise, personal motivation related to behavioral skills ( r = 0.53, p < .001), and behavioral skills related to behavior ( r = 0.45, p < .001). The IMB model could inform interventions targeting these behaviors in diabetes.
Predicting Condom Use among STD Clinic Patients Using the Information - Motivation-Behavioral Skills (IMB) Model
Authors: Scott-Sheldon Lori A.J. , Carey Michael P. , Vanable Peter A. , Senn Theresa E. , Coury-Doniger Patricia , Urban Marguerite A.
Published: May 2010

We assessed determinants of condom use postulated by the IMB model among STD patients ( N = 1474). The model provided acceptable fit to the data (CFI = 0.99, RMSEA = .04). Information was unrelated to condom use but had a negative effect on behavioral skills. Motivation had a positive effect on behavioral skills and condom use. Behavioral skills had a positive effect on condom use. In multiple-groups analyses, stronger associations between motivation and condom use were found among participants reporting no prior STD treatment. Interventions among STD patients should include activities addressing condom use motivation and directly enhancing condom skills.
Integrated Behavior Therapy in the Treatment of Complicated Tourette’s Disorder and Its Comorbidities
Authors: Bryson W. Jeff , Edwards Christopher L. , Sommer David B. , Scott Burton L.
Published: May 2010

Gilles de la Tourette’s syndrome (GTS) is a neuropsychiatric disorder that often presents with a complex array of motor and phonic tics that persist over the majority of a person’s life. GTS often presents with comorbidities such as attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and mood disorders. Psychosocial sequelae are also common among this population. We present the case of a 49-year-old woman with severe, lifelong GTS complicated by OCD, inattention, impulsivity, disinhibition, mood disturbances, generalized anxiety, and pain secondary to motor tics. Habit reversal therapy (HRT) is used with full body relaxation conditioned as a competitive response to target her tics, anxiety, and pain simultaneously. The patient demonstrates significant reduction of symptoms and improvement in psychosocial status within four sessions. She is able to maintain this status at a 3-month follow-up session. Aspects of case conceptualization and therapeutic technique are discussed.
Predictors of Response to Treadmill Exercise in Stroke Survivors
Authors: Lam Judith M. , Globas Christoph , Cerny Joachim , Hertler Benjamin , Uludag Kamil , Forrester Larry W. , Macko Richard F. , Hanley Daniel F. , Becker Clemens , Luft Andreas R.
Published: May 2010

Background. Aerobic treadmill exercise (T-EX) therapy has been shown to benefit walking and cardiorespiratory fitness in stroke survivors with chronic gait impairment even long after their stroke. The response, however, varies between individuals. Objective . The purpose of this post hoc analysis of 2 randomized controlled T-EX trials was to identify predictors for therapy response. Methods. In all, 52 participants received T-EX for 3 (Germany) or 6 (United States) months. Improvements in overground walking velocity (10 m/6-min walk) and fitness (peak VO2) were indicators of therapy response. Lesion location and volume were measured on T1-weighted magnetic resonance scans. Results . T-EX significantly improved gait and fitness, with gains in 10-m walk tests ranging between +113% and −25% and peak VO2 between −12% and 88%. Baseline walking impairments or fitness deficits were not predictive of therapy response; 10-m walk velocity improved more in those with subcortical rather than cortical lesions and in patients with smaller lesions. Improvements in 6-minute walk velocity were greater in those with more recent strokes and left-sided lesions. No variable other than training intensity, which was different between trials, predicted fitness gains. Conclusions. Despite proving overall effectiveness, the response to T-EX varies markedly between individuals. Whereas intensity of aerobic training seems to be an important predictor of gains in cardiovascular fitness, lesion size and location as well as interval between stroke onset and therapy delivery likely affect therapy response. These findings may be used to guide the timing of training and identify subgroups of patients for whom training modalities could be optimized.
Player, Student, Designer: Games Design Students and Changing Relationships With Games
Authors: Ashton Daniel
Published: May 2010

Drawing on empirical research conducted with U.K. games design students, games design course tutors, and professional designers alongside broader careers advice and guidance from industry representatives, this article will explore the changing relationships games design students describe with digital games and games technologies. Opening with accounts of their childhood pastimes and passions, the discussion will move to consider closely students’ development within a higher education context and the associated, emerging shifts in their engagements with games technologies. Through exploring the transition from hobby to career and the overlapping player/student/designer positions, questions concerning human and technological interactions, identity, and wider career and skills contexts are highlighted. In drawing out such questions and issues, this article will seek to outline how exploring the practices and understandings of students prompts reflection on both located and specific and more broadly applicable engagements between digital games technologies, industry, and individuals.
Computer Games and Sociocultural Play: An Activity Theoretical Perspective
Authors: Chee Siang Ang  , Zaphiris Panayiotis , Wilson Stephanie
Published: May 2010

Various forms of play emerge around computer games. These types of play, known as out-of-game play or extrinsic play, take place beyond the original game context. Despite their significant contribution to the overall play experience, they are often neglected by the game research community. Conventional game theories such as ludology and narratology do not provide an insightful account of the sociocultural aspects of game play. Therefore, in this article, we report our observations and investigations into different forms of extrinsic play activities in an online virtual setting. Founded on activity theory, we articulate theoretical models that explicate game play in a sociocultural context. Our findings reveal that extrinsic play constitutes reflective play and expansive play, which transform the play activity and transport the players beyond the original boundary of play.
What Is Video Game Culture? Cultural Studies and Game Studies
Authors: Shaw Adrienne
Published: May 2010

What is video game culture, however? What does it mean to have a culture defined by the consumption of a particular medium? Moreover, what are the implications of defining this culture in a particular way? While there has been a great deal of ink split on video game culture, the actual definition of the term is often treated as common sense. Unpacking the discourses surrounding ‘‘video game culture’’ allows us to see the power dynamics involved in attributing certain characteristics to it, as well as naming it ‘‘video game culture’’ as such. This has implications for how video games are studied and is connected with how culture is studied more broadly. By critically examining how video game culture has been defined in both press and academic articles, this paper illuminates how this definition has limited the study of video games and where it can move.
Cash Trade in Free-to-Play Online Games
Authors: Holin Lin  , Sun Chuen-Tsai
Published: May 2010

The rapidly expanding ‘‘free-to-play’’ online game payment model represents a huge shift in digital game commercialization, with cash payments for virtual items increasingly recognized as central to ‘‘free game’’ participation. In this article, the authors look at implications of this trend for gameplay experiences (especially in terms of immersion, fairness, and fun) and describe a fundamental shift in player self-perceptions as consumers rather than members of a gaming community. This change is occurring at a time when the line separating game and physical worlds is becoming less distinct. The new business model entails a subtle but significant reduction in consumer rights awareness, which explains why some members of the greater gaming community are negotiating a new sense of fairness and arriving at a new consensus regarding legitimate gameplay.
Narrative Structures in Computer and Video Games: Part 1: Context, Definitions, and Initial Findings
Authors: Ip Barry
Published: May 2010

This essay is the first of a two-part article examining the use of narrative in computer and video games, which provides an overview and discussion of the definitions and representation of stories, plots, and narratives. A range of traditional and emerging narrative techniques are considered, including The Hero’s Journey, three-act structure, the portrayal of human emotions, and character archetypes, from where an in-depth examination of interactive narrative is performed on a range of old and modern games. Initial results pertaining to the time allocated to narrative, the use of back stories, cut scenes, on-screen text, prompts, and game structure are also presented, which reveal a distinct level of uniformity of how interactive narrative is depicted in games spanning over two decades of industry development. The analysis is concluded in the second article, where further results are revealed to help uncover the precise nature of game narratives.
Behind the Avatar: The Patterns, Practices, and Functions of Role Playing in MMOs
Authors: Williams Dmitri , Kennedy Tracy L. M. , Moore Robert J.
Published: May 2010

A two-part quantitative and qualitative study of role players within a virtual game world examined their prevalence, practices, and identity formation. Drawing on unobtrusive behavioral data captured by the game, combined with a large survey and traditional ethnographic methods, the study found that role players both negotiate identity and use their time online as a moratorium for their offline lives.

Descriptive results showed that role players are a relatively small, but psychologically burdened subgroup. When examined from the theoretical perspectives of Goffman’s Self-Presentation theory, Huizenga’s Magic Circle, and Turkle’s early work on online identity formation, these players were seen as largely using virtual spaces as creative outlets and for socialization. The worlds also functioned as coping mechanisms for players frequently unable to gain acceptance, social connectivity or social support offline due to their personal situation, psychological profile, or their minority status.
Mental Health Benefits of Strength Training in Adults
Authors: O'Connor Patrick J. , Herring Matthew P. , Caravalho Amanda
Published: May 2010

This review summarizes evidence from randomized controlled trials to examine whether strength training influences anxiety, chronic pain, cognition, depression, fatigue symptoms, self-esteem, and sleep. The weight of the available evidence supported the conclusion that strength training is associated with reductions in anxiety symptoms among healthy adults (5 trials); reductions in pain intensity among patients with low back pain (5 trials), osteoarthritis (8 trials), and fibromyalgia (4 trials); improvements in cognition among older adults (7 trials); improvements in sleep quality among depressed older adults (2 trials); reductions in symptoms of depression among patients with diagnosed depression (4 trials) and fibromyalgia (2 trials); reductions in fatigue symptoms (10 trials); and improvements in self-esteem (6 trials). The evidence indicates that larger trials with a greater range of patient samples are needed to better estimate the magnitude and the consistency of the relationship between strength training and these mental health outcomes. Plausible social, psychological, and neural mechanisms by which strength training could influence these outcomes rarely have been explored. This review revealed the high-priority research need for animal and human research aimed at better understanding the brain mechanisms underlying mental health changes with strength training.
Like It! Learn It! Use It?
Authors: Frash Robert , Antun John , Kline Sheryl , Almanza Barbara
Published: May 2010

This field study examines factors influencing hotel employees’ ability to transfer the concepts that they learned in job training when they return to work. The study was conducted during a major hotel company’s training program. The training objective was to ready front-desk associates to operate a new property management system (PMS). Past business research suggests that trainee characteristics, training design, and work environment factors can positively impact an employee’s transfer of training. Role-play exercises and surveys were used to explore the validity of this research in a hospitality setting. This study’s findings suggest that proper management of these impact factors can foster enhanced transfer of training in hotels. Strategies are offered to help hospitality human resource professionals improve training transfer in hotels.
Arthroscopic Treatment of Femoroacetabular Impingement in Patients over 60 Years Old: Preliminary Report of a Pilot Study
Authors: Mardones Rodrigo M. , Nemtala Fernando , Tomic Alexander
Published: May 2010

The objective was to evaluate short-term outcomes of patients of more than 60 years old, who underwent arthroscopic treatment for femoroacetabular impingement (FAI). The study design was a nonrandomized controlled clinical trial; this was a prospective study in 15 patients (15 hips) over 60 years old. Inclusion criteria were symptomatic FAI, no prior surgeries of the affected hip, and osteoarthritis Tonnis classification grade I or II. Exclusion criteria were multiple or large (≥5 mm) chondral defects or subchondral bone cysts in the acetabulum or the femoral head seen on magnetic resonance imaging (MRI). Radiographs and MRI arthrograms were used for the imaging assessment in all cases. Procedures performed arthroscopically included labrum resection, acetabuloplasty, and femoral osteoplasty in all cases. The Harris Hip Score was applied preoperatively and 2 years postoperatively. At 2 years postoperatively, the average increase in the Harris Hip Score was 21 points (mainly pain reduction) from a mean preoperative score of 66 points to a mean postoperative score of 87 points; this difference was significant (P < 0.05). Three cases (20%) had poor outcomes and required a total hip replacement during the first year after the surgery. Poor results were associated with Tonnis grade II osteoarthritis and Outerbridge grade III or IV chondral defects. Arthroscopic treatment of FAI of patients over 60 years old showed a significant Harris Hip Score increase as a result of excellent and good short-term clinical results in most of the patients of our study. Nevertheless, despite strict selection criteria for very well-selected patients, we observed an early failure rate of up to 20%.
Extracellular protein disulfide isomerase regulates coagulation on endothelial cells through modulation of phosphatidylserine exposure
Authors: Popescu Narcis I. , Lupu Cristina , Lupu Florea
Published: May 2010

Tissue factor (TF) is the cellular receptor for plasma protease factor VIIa (FVIIa), and the TF-FVIIa complex initiates coagulation in both hemostasis and thrombosis. Cell surface-exposed TF is mainly cryptic and requires activation to fully exhibit the procoagulant potential. Recently, the protein disulfide isomerase (PDI) has been hypothesized to regulate TF decryption through the redox switch of an exposed disulfide in TF extracellular domain. In this study, we analyzed PDI contribution to coagulation using an in vitro endothelial cell model. In this model, extracellular PDI is detected by imaging and flow cytometry. Inhibition of cell surface PDI induces a marked increase in TF procoagulant function, whereas exogenous addition of PDI inhibits TF decryption. The coagulant effects of PDI inhibition were sensitive to annexin V treatment, suggesting exposure of phosphatidylserine (PS), which was confirmed by prothrombinase assays and direct labeling. In contrast, exogenous PDI addition enhanced PS internalization. Analysis of fluorescent PS revealed that PDI affects both the apparent flippase and floppase activities on endothelial cells. In conclusion, we identified a new mechanism for PDI contribution to coagulation on endothelial cells, namely, the regulation of PS exposure, where PDI acts as a negative regulator of coagulation.
Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan
Authors: Iwanaga Masako , Watanabe Toshiki , Utsunomiya Atae , Okayama Akihiko , Uchimaru Kaoru , Koh Ki-Ryang , Ogata Masao , Kikuchi Hiroshi , Sagara Yasuko , Uozumi Kimiharu , Mochizuki Manabu , Tsukasaki Kunihiro , Saburi Yoshio , Yamamura Masaomi , Tanaka Junji , Moriuchi Yukiyoshi , Hino Shigeo , Kamihira Shimeru , Yamaguchi Kazunari ,   for the Joint Study on Predisposing Factors of ATL Development investigators
Published: May 2010

Definitive risk factors for the development of adult T-cell leukemia (ATL) among asymptomatic human T-cell leukemia virus type I (HTLV-1) carriers remain unclear. Recently, HTLV-1 proviral loads have been evaluated as important predictors of ATL, but a few small prospective studies have been conducted. We prospectively evaluated 1218 asymptomatic HTLV-1 carriers (426 males and 792 females) who were enrolled during 2002 to 2008. The proviral load at enrollment was significantly higher in males than females (median, 2.10 vs 1.39 copies/100 peripheral blood mononuclear cells [PBMCs]; P < .001), in those 40 to 49 and 50 to 59 years of age than that of those 40 years of age and younger (P = .02 and .007, respectively), and in those with a family history of ATL than those without the history (median, 2.32 vs 1.33 copies/100 PBMCs; P = .005). During follow-up, 14 participants progressed to overt ATL. Their baseline proviral load was high (range, 4.17-28.58 copies/100 PBMCs). None developed ATL among those with a baseline proviral load lower than approximately 4 copies. Multivariate Cox analyses indicated that not only a higher proviral load, advanced age, family history of ATL, and first opportunity for HTLV-1 testing during treatment for other diseases were independent risk factors for progression of ATL.
Live imaging of Runx1 expression in the dorsal aorta tracks the emergence of blood progenitors from endothelial cells
Authors: Lam Enid Yi Ni , Hall Christopher J. , Crosier Philip S. , Crosier Kathryn E. , Flores Maria Vega
Published: May 2010

Blood cells of an adult vertebrate are continuously generated by hematopoietic stem cells (HSCs) that originate during embryonic life within the aorta-gonad-mesonephros region. There is now compelling in vivo evidence that HSCs are generated from aortic endothelial cells and that this process is critically regulated by the transcription factor Runx1. By time-lapse microscopy of Runx1-enhanced green fluorescent protein transgenic zebrafish embryos, we were able to capture a subset of cells within the ventral endothelium of the dorsal aorta, as they acquire hemogenic properties and directly emerge as presumptive HSCs. These nascent hematopoietic cells assume a rounded morphology, transiently occupy the subaortic space, and eventually enter the circulation via the caudal vein. Cell tracing showed that these cells subsequently populated the sites of definitive hematopoiesis (thymus and kidney), consistent with an HSC identity. HSC numbers depended on activity of the transcription factor Runx1, on blood flow, and on proper development of the dorsal aorta (features in common with mammals). This study captures the earliest events of the transition of endothelial cells to a hemogenic endothelium and demonstrates that embryonic hematopoietic progenitors directly differentiate from endothelial cells within a living organism.
Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors
Authors: Dudley Andrew C. , Udagawa Taturo , Melero-Martin Juan M. , Shih Shou-Ching , Curatolo Adam , Moses Marsha A. , Klagsbrun Michael
Published: May 2010

The hypothesis that bone marrow–derived, circulating endothelial cells incorporate into tumor blood vessels is unresolved. We have measured the numbers of bone marrow–derived versus resident endothelial cells in spontaneous prostate cancers during different stages of tumor progression and in age-matched normal prostates. Bone marrow–derived endothelial cells were rare in dysplasia and in well differentiated cancers representing between 0 and 0.04% of the total tumor mass. Instead, approximately 99% of all tumor-associated bone marrow–derived cells were CD45+ hematopoietic cells, including GR-1+, F4-80+, and CD11b+ myeloid cells. Similar to peripheral blood mononuclear cells, these tumor-associated myeloid cells expressed matrix metalloproteinases (MMPs), consistent with their proposed catalytic role during tumor angiogenesis. Furthermore, freshly isolated CD11b+ cells stimulated tumor endothelial cell cord formation by 10-fold in an in vitro angiogenesis assay. The bone marrow is, therefore, a reservoir for cells that augment tumor angiogenesis, but the tumor endothelium is derived primarily from the local environment.
Multigranular exocytosis of Weibel-Palade bodies in vascular endothelial cells
Authors: Valentijn Karine M. , van Driel Linda F. , Mourik Marjon J. , Hendriks Gert-Jan , Arends Tom J. , Koster Abraham J. , Valentijn Jack A.
Published: May 2010

Regulated exocytosis of Weibel-Palade bodies (WPBs) is a pivotal mechanism via which vascular endothelial cells initiate repair in response to injury and inflammation. Several pathways have been proposed to enable differential release of bioactive molecules from WPBs under different pathophysiologic conditions. Due to the complexity, many aspects of WPB biogenesis and exocytosis are still poorly understood. Herein, we have investigated the regulated exocytosis of the major WPB constituent, von Willebrand Factor (VWF), which upon its release forms strings of up to several millimeters long that capture circulating platelets and thereby initiate the formation of a haemostatic plug. Using correlative, fluorescence, and electron microscopic imaging techniques, we provide evidence that multigranular exocytosis is an important pathway for VWF release in secretagogue-challenged human umbilical vein endothelial cells. A novel membrane-delimited structure (secretory pod) was identified as the site of WPB coalescence and VWF exocytosis. Clathrin-coated profiles present on the secretory pods suggested remodeling via compensatory membrane retrieval. Small, 30- to 40-nm cytoplasmic vesicles (nanovesicles) mediated the fusion of WPBs with secretory pods. Multigranular exocytosis may facilitate VWF string formation by pooling the content of multiple WPBs. In addition, it may provide a novel mechanism for the differential release of WPB cargo.
Towards the systematic discovery of signal transduction networks using phosphorylation dynamics data
Authors: Imamura Haruna , Yachie Nozomu , Saito Rintaro , Ishihama Yasushi , Tomita Masaru
Published: May 2010

Background

Phosphorylation is a ubiquitous and fundamental regulatory mechanism that controls signal transduction in living cells. The number of identified phosphoproteins and their phosphosites is rapidly increasing as a result of recent mass spectrometry-based approaches.

Results

We analyzed time-course phosphoproteome data obtained previously by liquid chromatography mass spectrometry with the stable isotope labeling using amino acids in cell culture (SILAC) method. This provides the relative phosphorylation activities of digested peptides at each of five time points after stimulating HeLa cells with epidermal growth factor (EGF). We initially calculated the correlations between the phosphorylation dynamics patterns of every pair of peptides and connected the strongly correlated pairs to construct a network. We found that peptides extracted from the same intracellular fraction (nucleus vs. cytoplasm) tended to be close together within this phosphorylation dynamics-based network. The network was then analyzed using graph theory and compared with five known signal-transduction pathways. The dynamics-based network was correlated with known signaling pathways in the NetPath and Phospho.ELM databases, and especially with the EGF receptor (EGFR) signaling pathway. Although the phosphorylation patterns of many proteins were drastically changed by the EGF stimulation, our results suggest that only EGFR signaling transduction was both strongly activated and precisely controlled.

Conclusions

The construction of a phosphorylation dynamics-based network provides a useful overview of condition-specific intracellular signal transduction using quantitative time-course phosphoproteome data under specific experimental conditions. Detailed prediction of signal transduction based on phosphoproteome dynamics remains challenging. However, since the phosphorylation profiles of kinase-substrate pairs on the specific pathway were localized in the dynamics-based network, our method will be a complementary strategy to explore new components of protein signaling pathways in combination with previous methods (including software) of predicting direct kinase-substrate relationships.
Identification of genetic modifiers of behavioral phenotypes in serotonin transporter knockout rats
Authors: Homberg Judith , Nijman Isaäc J , Kuijpers Sylvia , Cuppen Edwin
Published: May 2010

Background

Genetic variation in the regulatory region of the human serotonin transporter gene (SLC6A4) has been shown to affect brain functionality and personality. However, large heterogeneity in its biological effects is observed, which is at least partially due to genetic modifiers. To gain insight into serotonin transporter (SERT)-specific genetic modifiers, we studied an intercross between the Wistar SERT-/- rat and the behaviorally and genetically divergent Brown Norway rat, and performed a QTL analysis.

Results

In a cohort of >150 intercross SERT-/- and control (SERT+/+) rats we characterized 12 traits that were previously associated with SERT deficiency, including activity, exploratory pattern, cocaine-induced locomotor activity, and abdominal and subcutaneous fat. Using 325 genetic markers, 10 SERT-/--specific quantitative trait loci (QTLs) for parameters related to activity and exploratory pattern (Chr.1,9,11,14), and cocaine-induced anxiety and locomotor activity (Chr.5,8) were identified. No significant QTLs were found for fat parameters. Using in silico approaches we explored potential causal genes within modifier QTL regions and found interesting candidates, amongst others, the 5-HT1D receptor (Chr. 5), dopamine D2 receptor (Chr. 8), cannabinoid receptor 2 (Chr. 5), and genes involved in fetal development and plasticity (across chromosomes).

Conclusions

We anticipate that the SERT-/--specific QTLs may lead to the identification of new modulators of serotonergic signaling, which may be targets for pharmacogenetic and therapeutic approaches.
Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes
Authors: Chen Jianshun , Chen Qiaomiao , Jiang Lingli , Cheng Changyong , Bai Fan , Wang Jun , Mo Fan , Fang Weihuan
Published: May 2010

Background

Ecological, biochemical and genetic resemblance as well as clear differences of virulence betweenL. monocytogenesandL. innocuamake this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure ofL. innocuaand the microevolution in theL. innocua-L. monocytogenesclade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genesgyrB,sigB,dapE,hisJ,ribC,purM,gap,tufandbetL.

Results

L. innocuawas genetically monophyletic compared toL. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C) and internalin types 2 and 4 respectively. The majority ofL. innocuastrains belonged to these two subgroups. Subgroup A harbored a whole set ofL. monocytogenes-L. innocuacommon andL. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (ρ/θ) and the relative effect of recombination versus point mutation (r/m). Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA) ofL. innocuasubgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. AllL. innocuastrains lacked seventeen virulence genes found inL. monocytogenes(except for the subgroup D strain L43 harboringinlJand two subgroup B strains bearingbsh) and were nonpathogenic to mice.

Conclusions

L. innocuarepresents a young species descending fromL. monocytogenesand comprises four subgroups: two major subgroups A and B, and one atypical subgroup D serving as a link betweenL. monocytogenesandL. innocuain the evolutionary chain. Although subgroups A and B appeared at approximately the same time, subgroup A seems to have experienced a recent expansion of the population size with higher recombination frequency and effect than those of subgroup B, and might represent the possible evolutionary direction towards adaptation to enviroments. The evolutionary history in theL. monocytogenes-L. innocuaclade represents a rare example of evolution towards reduced virulence of pathogens.
Loss of phosphoinositide 3-kinase γ decreases migration and activation of phagocytes but not T cell activation in antigen-induced arthritis
Authors: Gruen Michael , Rose Christina , König Christian , Gajda Mieczyslaw , Wetzker Reinhard , Bräuer Rolf
Published: May 2010

Background

Phosphoinositide 3-kinase γ (PI3Kγ) has been depicted as a major regulator of inflammatory processes, including leukocyte activation and migration towards several chemokines. This study aims to explore the role of PI3Kγ in the murine model of antigen-induced arthritis (AIA).

Methods

Development of AIA was investigated in wildtype and PI3Kγ-deficient mice as well as in mice treated with a specific inhibitor of PI3Kγ (AS-605240) in comparison to untreated animals. Inflammatory reactions of leukocytes, including macrophage and T cell activation, and macrophage migration, were studiedin vivoandin vitro.

Results

Genetic deletion or pharmacological inhibition of PI3Kγ induced a marked decrease of clinical symptoms in early AIA, together with a considerably diminished macrophage migration and activation (lower production of NO, IL-1β, IL-6). Also, macrophage and neutrophil infiltration into the knee joint were impairedin vivo. However, T cell functions, measured by cytokine production (TNFα, IFNγ, IL-2, IL-4, IL-5, IL-17)in vitroand DTH reactionin vivowere not altered, and accordingly, disease developed normally at later timepoints

Conclusion

PI3Kγ specifically affects phagocyte function in the AIA model but has no impact on T cell activation.