bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognition of Social Capital in Older Japanese Men and Women
Authors: Aihara Yoko , Minai Junko , Kikuchi Yuki , Aoyama Atsuko , Shimanouchi Setsu
Published: October 2009

Objective: This study explored factors related to cognition of social capital among Japanese older people. Method: Using a cross-sectional survey design, data were gathered from 940 people aged over 65 years. Cognition of social capital was compared by gender, and it was regressed on participation in community activities and health behaviors of middle age and current health status. Results: Men had higher cognitive social capital than women ( p = .004). Multiple regression analysis shows that men who rested for health during middle age had high cognition of social capital. Cognition of social capital was also related to self-rated health, depression, and cognitive difficulties for both men and women. Daily activity was included among women. Discussion: Participation in community activities and health behaviors during middle age were associated factors for cognition of social capital among the older people, and encouraging cognition of social capital was important for active aging.
Exploring Family Management of Childhood Brain Tumor Survivors
Authors: Deatrick Janet A. , Mullaney Erin K. , Mooney-Doyle Kim
Published: October 2009

Family management of childhood chronic conditions consists of 6 family factors: (1) the family’s view of the child’s daily life, (2) the impact of the condition on family life, (3) the difficulty of family life, (4) the family’s effort managing the child’s condition, (5) the family’s ability managing the child’s condition, and (6) parental mutuality. Recently, the Family Management Measure (FaMM), which measures family management of children with chronic conditions (excluding cancer), was validated. The purpose of this descriptive study was to examine the comparability of these 6 factors in families with childhood brain tumor survivors. First, 14 advanced practice nurses who are experts in neuro-oncology and survivorship rated items on the FaMM as relevant and clear to families of brain tumor survivors. Second, 22 cognitive interviews with parents of brain tumor survivors described family management as comparable with families of children with other chronic illness. In this report, 2 hypothetical, contrasting case studies of family management are used to illustrate family management within the context of brain tumor survivors.
How Children With Cancer Communicate and Think About Symptoms
Authors: Vatne Torun M. , Slaugther Laura , Ruland Cornelia M.
Published: October 2009

Background. For clinicians to effectively help children with their illness and symptoms, it is important to communicate with them in a language they can understand. Methods. This study investigates how well children with cancer and healthy children understood 44 symptom terms; their thoughts about these symptoms in terms of causes, consequences, and cures; and what other terms the children use to express these symptoms. It also explores if there are differences in understanding and thoughts about symptoms between children who have the experience of cancer and those who do not. In all, 6 children with cancer and 8 healthy children participated in semistructured interviews. Results. Children demonstrated a good understanding of symptom terms, yet were not always able to explain the symptoms. They had a rich vocabulary to talk about symptoms but did not use childish terms. Children with cancer had a more varied vocabulary for symptoms, but they did not use more medical terms.This study contributes to knowledge about children’s understanding of symptoms that can be helpful to clinicians when communicating with children about their illness.
Externalities in Exchange Networks
Authors: Dijkstra Jacob
Published: October 2009

The present paper extends the focus of network exchange research to externalities in exchange networks. Externalities of exchange are defined as direct effects on an actor’s utility, of an exchange in which this actor is not involved. Existing theories in the field of network exchange do not inform us on how externalities are predicted to affect behavior in exchange networks. Three prominent theories in the field, core theory, power dependence theory and exchange resistance theory, are extended to exchange networks with externalities, allowing three main conclusions about the expected effects of externalities in exchange networks: externalities (i) change actors’ payoffs, (ii) change the exchange pattern, and (iii) change the power distribution across actors. The investigated theories yield predictions concerning the occurrence and magnitude of these effects. A method is proposed to separate the effect of (i) the network, (ii) the externalities, and (iii) the interaction between network and externalities.
Low Dose of Argatroban Saline Flushes Anticoagulation in Hemodialysis Patients With High Risk of Bleeding
Authors: Zhang Yixiong  , Ning Jianping  , Li Yanchao  , Dai Siyuan
Published: October 2009

Background: Anticoagulation in hemodialysis (HD) patients with high risk of bleeding is still an intractable problem. Method: A total of 80 HD sessions with high risk of bleeding were completed with either heparin-free (HF) or low dose of argatroban saline flushes (LASF) anticoagulation. Clinical clot formation in the pipeline and dialyzer was inspected to evaluate the local anticoagulation efficiency; prothrombin time (PT), activated partial thromboplastin time (aPTT), and D-dimer were tested to investigate the influence on the whole body coagulation system; urea reduction ratio (URR) and Kt/V were used to evaluate the efficiency of dialysis. Results: Comparing with HF, LASF showed a satisfactory efficiency in reducing the clot formation and the URR and Kt/V of it were also higher. Conclusions: Low dose of argatroban saline flushes is a feasible and safe alternative anticoagulation protocol in HD patients with high risk of bleeding.
Clinical Studies of Laser Ablation in Treatment of Primary Liver Carcinoma-Associated Portal Vein Tumor Thrombus
Authors: Baomu Sun  , Ming Luo  , Zhenghua Lu  , Yan Meng  , Shengbing Wu  , Mengchao Wu
Published: October 2009

Objective: To explore the clinical values of laser ablation as a new treatment for portal vein tumor thrombus (PVTT). Methods: A total of 43 male patients with primary liver carcinoma (PLC)-associated PVTT were randomized into a laser ablation group and a radiotherapy group. The laser ablation group of 21 cases received direct percutaneous laser ablation under ultrasonographic guide, followed by direct injection into the portal vein with chemotherapy drugs including mitomycin C (MMC) and fluorouracil (5-Fu). The radiotherapy group of 22 cases was treated with X-ray in three-dimensional conformal radiotherapy (3D CRT) once a day for a total of 10 days course. After the treatment, all patients were followed for postoperative adverse reactions, changes of tumor thrombus, and survival time. Results: In comparison with the radiotherapy, laser ablation resulted in decreased postoperative complications such as limb fatigue, ascites, upper gastrointestinal ulcer, and bleeding. The overall remission rates (complete remission [CR] + partial remission [PR]) were 61.9% (13/21) and 31.8% (7/22) in the laser ablation and radiotherapy group, respectively, with a significant difference (P < .05). All cases in the laser group showed clinical improvement and the average survival time prolonged to greater than 19.5 months (P < .002). Conclusion: Percutaneous laser ablation to PVTT is an effective, safe, and simply procedure and has proven to offer significant clinical outcomes in the treatment of PLC-associated PVTT.
Assessment of the Usefulness of Antithrombin-III in the Management of Disseminated Intravascular Coagulation in Obstetrically Ill Patients
Authors: Kobayashi Aiko , Matsuda Yoshio , Mitani Minoru , Makino Yasuo , Ohta Hiroaki
Published: October 2009

Objective: The aim of this study was to analyze the antithrombin-III (AT-III) activity in the serum in relation to other laboratory findings, including the serum albumin, total protein (TP), and uric acid (UA), and to assess the recovery of the AT-III activity in the serum after its administration in obstetrically ill patients. Patients and Methods: The medical records of 27 patients who were diagnosed to have disseminated intravascular coagulation (DIC) based on the obstetric DIC scores were reviewed and the relationships between the activity of AT-III in the serum and other laboratory findings were evaluated. The effect of administration of AT-III on the recovery of AT-III activity in the serum was also evaluated. Results: All the patients survived without any sequelae. The mean obstetric DIC score was 11.1 ± 3.1 (range 8-19) and the mean blood loss during the first 24 hours was 3798 ± 3,435 mL (range 480-16 208 mL). There was a significant correlation between the serum AT-III activity before the treatment and the serum albumin (r = .67, P = .001) and TP (r = .59, P = .021), but not serum UA. Seven patients required over 3000 IU of AT-III concentrate to obtain an increase in the serum AT-III activity to over 70%. The UA level in this group was significantly higher than that in the remaining patients. Conclusion: The serum AT-III activity was correlated with the serum albumin level before the start of treatment. Therefore, measurement of the serum albumin level before and during treatment is helpful.
Candidate Genes of Cerebrovascular Disease and Sudden Sensorineural Hearing Loss
Authors: Um Jae-Young , Jang Chul-Ho , Kim Kyu-Yeob , Kim Su-Jin , Kim Na-Hyung , Moon Phil-Dong , Choi In-Young , Myung Noh-Yil , Jeong Hyun-Ja , Hong Seung-Heon , Kim Hyung-Min
Published: October 2009

Auditory dysfunction is related to large/small vessel occlusions and hemorrhage. Sudden sensorineural hearing loss (SSNHL) frequently occurs with anterior inferior cerebellar artery occlusion proximal to the internal auditory artery. Moreover, SSNHL has various pathogenetic mechanisms, the main proposed mechanisms being vascular disease, membrane ruptures, infection, and autoimmunity. Tumor necrosis factor (TNF) is an important cytokine in the inflammation process of cerebrovascular diseases. In the current study, the possible effects of polymorphisms in TNF-α and TNF-β genes on SSNHL are evaluated. Two genetic polymorphisms in the TNF locus (TNF-α —308 G - ->A and TNF-β +252 A - ->G) were investigated as risk factors for SSNHL by determining their prevalence in 97 SSNHL patients and in 587 controls. A significant increase was found for the TNF-β allele 1 in SSNHL patients compared with the controls (χ 2 = 7.251, P = .007, odds ratio [OR] = 1.534, confidence interval [CI] = 1.12-2.10). These findings suggest that the TNF-β +252 locus plays an important role in the etiopathogenesis of SSNHL.
Meta-Analysis of Association Between Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene and Venous Thromboembolism
Authors: Hsiao Fu-Chih , Hsu Lung-An
Published: October 2009

An insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene accounts for 50% of the interindividual serum ACE level variation. Because the renin—angiotensin system regulates coagulation and vasoconstriction, it could have a role in venous thromboembolism (VTE). Several studies have evaluated the relationship between ACE I/D polymorphism and VTE, although the findings have been controversial. We performed a meta-analysis by pooling data from 14 studies. Publication bias was not observed. The current study did not support any association between the DD genotype and VTE. The pooled odds ratio (ORp) was 1.206; 95% confidence interval (CI), 0.951-1.531; P = .123. Similar results were obtained when the effects of the D allele were assumed to be dominant (DD and ID vs II; ORp = 1.127, 95% CI, 0.902-1.409). Our data do not support the inclusion of ACE I/D polymorphism testing in clinical thrombophilia workups until more compelling data are made available.
Gendering Coercive Control
Authors: Anderson Kristin L.
Published: October 2009

This article examines the theory of gender presented in Stark’s Coercive Control: How Men Entrap Women in Personal Life. Stark suggests that gender is a form of structural inequality that makes women more vulnerable than men to the strategies of coercive control. However, Stark assumes rather than demonstrates that gendered structural inequality increases women’s vulnerability. In this article, the author applies the multilevel theory of gender as identity, interaction, and social structure to document the multiple ways coercive control is gendered. The author argues that, to understand the gender dynamics of coercive control, researchers must examine the interactions across levels of gender. The author concludes with an assessment of the prospects and pitfalls of applying the concept of coercive control to renew the feminist social movement to end domestic violence.
Reframing Violence Against Women as a Human Rights Violation: Evan Stark’s Coercive Control
Authors: Libal Kathryn , Parekh Serena
Published: October 2009

Evan Stark claims that partner-perpetrated physical abuse and other forms of violence against women ought to be understood as a human rights violation. The authors engage Stark’s rhetorically powerful political and analytical innovation by outlining one theoretical and one practical challenge to shifting the paradigm that researchers, advocates, and policy makers use to describe, explain, and remedy the harms of coercive control from misdemeanor assault to human rights violation. The theoretical challenge involves overcoming the public/ private dichotomy that underpins liberal conceptions of human rights.The practical challenge involves using the human rights framework in the United States, given public indifference to human rights rhetoric or law, reluctance of U.S. policy makers to submit to scrutiny or justice-oriented processes under international law on issues of human rights and especially war crimes, and the consequent U.S. legacy of refusal to participate meaningfully in the international human rights process. The authors conclude that employing a human rights framework holds potential in the United States, but the paradigm shift Stark advocates will not materialize without widespread mobilization of interest in and understanding of human rights among domestic violence advocates and the society in general.
Glucarpidase rescue in a patient with high-dose methotrexate-induced nephrotoxicity
Authors: Tuffaha Haitham W , Al Omar Suha
Published: October 2009

Purpose. To describe the successful use of glucar- pidase (carboxypeptidase G2) in the treatment of high-dose methotrexate-induced nephrotoxicity in a patient with osteosarcoma.

Summary. A 12-year-old female patient who had been diagnosed with low-grade right mandibular osteosarcoma was started on a protocol of cisplatin plus doxorubicin alternating with high-dose metho- trexate. Following her first dose of methotrexte, she developed acute renal failure and higher than expected 24h methotrexate level of 478μM/L. High-dose leucovorin rescue was started with vigorous hydra- tion and urine alkalinization together with two sessions of hemodialysis. Because her methotrexate level was persistently high, the investigational drug glucarpidase was administered. Methotrexate leveldropped from 65 to 16.3 μM/L after a single dose of glucarpidase measured by fluorescence polarization immunoassay. Leucovorin and urine alkalinization were continued until day 17 when the patient’s kidney function normalized and methotrexate level reached 0.05 μM/L. The patient tolerated glucarpidase well without any significant adverse events.

Conclusion. Glucarpidase is a safe and effective agent in the management of high-dose methotrexate-induced nephrotoxicity and delayed methotrexate elimination. J Oncol Pharm Practice (2011) 17: 136—140.
Capecitabine-induced cerebellar toxicity in a patient with metastatic colorectal cancer
Authors: Gounaris Ioannis , Ahmad Athar
Published: October 2009

Introduction. Capecitabine is an oral fluoropyrimidine that was designed to allow selective activation in tumour tissues, thus reducing toxicity. The neurologic toxicity of 5-fluorouracil, the original fluoropyrimidine, including an ataxic cerebellar syndrome is well described. However, only a few case reports exist describing a similar syndrome associated with capecitabine administration.

Case Report. We report a case of reversible cerebellar toxicity during chemotherapy with a combination of capecitabine and oxaliplatin.

Discussion. Rare fluoropyrimide-related toxicities are increasingly being reported in association with capecitabine. Clinical vigilance is required to ensure appropriate investigation and treatment.
Chromatic Changes in Broccoli (Brassica oleracea italica) under Modified Atmospheres in Perforated Film Packages
Authors: Rai D.R. , Jha S.N. , Wanjari O.D. , Patil R.T.
Published: October 2009

Broccoli was stored under modified atmosphere packaging (MAP) at 20 °C in perforated and unsealed polypropylene film packages for a storage period of 10 days to evaluate the effect of modified atmospheres on the chromatic changes. At the end of storage, MAP resulted in differential changes in the original green color of broccoli under different packaging treatments. Instead of conventional CIELAB color space system utilizing only L*, a* and b* values, the chromatic changes were analyzed as per L*C*h* color space system using lightness, chroma, and hue angle values to evaluate the final hue (color) along with its associated attributes. On 10th day of storage, broccoli samples kept under different modified atmospheres were observed to be yellow-green only for 4 holes, but between yellow-green and yellow for 8, 12, and 16 hole treatments, respectively. Further, the saturation of final hue attained under different packaging treatments kept on increasing in the order of 4, 8, 12, and 16 holes. On the other hand, broccoli kept in air in unsealed packages turned orange-yellow with higher saturation as compared with MAP samples. The direction of color difference for different treatments with respect to fresh broccoli samples was observed as light and the degree of color difference indicated that 4 and 8 hole treatments were only slight and medium light, respectively. The 4 hole treatment had best color retention as it had slightly saturated yellow-green hue, which was only slightly lighter than the fresh broccoli. Also, the results of sensory and visual analysis confirmed the results obtained from L*C*h* color space diagram and indicated that the modified atmosphere (6.1% O2 and 9% CO2) generated inside the perforated film packages having 4 macro-holes was the most suitable in maintaining the chromatic quality of the broccoli heads.
A Model for Statewide Evaluation of a Universal Positive Behavior Support Initiative
Authors: Elfner Childs Karen , Kincaid Don , Peshak George Heather
Published: October 2009

Several statewide evaluations of Tier 1/Universal Level Positive Behavior Support (PBS) implementation efforts have been conducted, adhering to the evaluation template developed by Horner, Sugai, and Lewis-Palmer in 2005. Building on these examples, Florida’s Positive Behavior Support Project developed a comprehensive evaluation system that sought to answer critical questions about building a scalable and sustainable PBS system at the state level that also provides data for decision making at the school and district levels. This article describes Florida’s evaluation system as a model driven by 12 questions, including topics of implementation fidelity as both a dependent and independent variable, and expanding traditional questions of statewide evaluations to include consumer satisfaction, team processes, barriers and facilitators to implementation, and attrition. The data indicated that implementing Tier 1/Universal Level PBS with fidelity was associated with improved student outcomes. Additional findings are described as are considerations for future directions.
Experiencing the Shadow: Organizational Exclusion and Denial within Experience Economy
Authors: Kociatkiewicz Jerzy , Kostera Monika
Published: October 2009

This article focuses on the dark and hidden aspects of experience economy events. These aspects are framed as the shadow in the Jungian sense, i.e. an archetype of the unconscious domain. Individuals and organizations create a shadow as a side effect of attempts at control and ordering of their identity. The article presents stories based on ethnographically inspired field studies of experience economy events to show how staged experience produces an experiential shadow side. The process is problematized and reflected upon as a shadow producing side effect of identity production and management in experience economy settings. The possibilities for the integration of the shadow into the normal operation of experience economy organizations are considered with the help of images of the carnival and the archetype the fool. The acceptance of the paradoxical and strange side of such events they may be better understood and their dark side integrated.
Re-imagining E-mail: Academics in The Castle
Authors: Keenoy Tom , Seijo Gustavo
Published: October 2009

Starting out from Franz Kafka’s novel, The Castle , we meander through an exploration of the impact of that seminal socio-digital artefact—e-mail—on the academic lifeworld. In the process, we illustrate not only how e-mail is ‘experienced’, facilitates instantaneity, deludes us with speed, shapes the working day and accelerates work processing but also the ultimately illusory promise of the ‘wired’ world to empower us to escape organizational boundaries. Paradoxically, the Castle is always one step behind but it never comes second.
Use of the Cultural Formulation with Refugees
Authors: Rohlof Hans , Knipscheer Jeroen W. , Kleber Rolf J.
Published: October 2009

This article discusses the experiences of mental health professionals who applied the Cultural Formulation (CF) of the DSM-IV for assessment of psychopathology and treatment needs of refugees in the Netherlands. The CF approach proved to be a useful tool in the assessment and diagnostic phase of clinical treatment. However, patients reported problems with defining their own culture and providing explanations of illness and therapists had difficulty identifying culturally-based difficulties in the clinical relationship. Additional information was needed about working with interpreters, therapists’ attitudes towards the culture of the patient and towards their own culture, patients’ previous experiences with discrimination and inaccessibility of care, gender issues, and specific cultures and subcultures. A more structured approach to conducting the CF is recommended. We developed the “Cultural Formulation Interview” for this purpose. The adaptations are aimed at improving the CF for use with refugee populations, as well as for more general use in transcultural psychiatry.
DSM-IV-TR Cultural Formulation of Psychiatric Cases: Two Proposals for Clinicians
Authors: Caballero Martínez Luis
Published: October 2009

This article reviews some limitations of the current guideline for the DSM-IV-TR Cultural Formulation (CF) from the perspective of psychiatric practice that are based on the author’s experience conducting doctoral courses on cultural psychiatry from 1996 to 2007 in the Department of Psychiatry at the Universidad Autónoma de Madrid (Spain). Two proposals are presented for facilitating use of the CF by general clinicians. These proposals offer a procedure for embedding only the most relevant clinical information in a psychiatric history, followed by a brief cultural formulation. The approach is illustrated with a clinical case. Although the CF has considerable promise for revealing knowledge about patients, health practices, and health systems that is essential for clinical care, substantial research must be carried out to facilitate widespread use of the CF in clinical practice.
The association of continuity of care on the diagnosis of hypertension in children and adolescents
Authors: Benson Lacey J. , Cohn Robert , Kaelber David C.
Published: October 2009

Hypertension among pediatric patients is an underdiagnosed condition. As continuity of care has been found to increase quality of pediatric care, we undertook this study to assess effect of continuity on diagnosis of pediatric hypertension. This is a retrospective analysis of 774 hypertensive patients, ages 3—18 years between June 1999 and October 2007 within the MetroHealth System in northeastern Ohio. The proportion of hypertensive patients diagnosed was assessed using coding within the electronic medical record. Continuity was assessed using the usual provider of care, defined as the number of visits to the most frequent provider divided by the total number of visits in the study period. Overall continuity did not have a statistically significant association with diagnosis (OR 0.7, CI 0.4—1.4). Our research indicates that continuity does not significantly affect diagnosis of hypertension in pediatric patients. Other approaches should be investigated to improve the significant underdiagnosis of pediatric hypertension.
Children’s tonsillectomy experiences: influencing factors
Authors: Crandall Margie , Lammers Cathy , Senders Craig , Braun Jerome V.
Published: October 2009

The aim of this study was to explore factors influencing children’s (7—13 years) tonsillectomy experiences and outcomes. A prospective, repeated measures, design was used to investigate the effect of age, gender, ethnicity, time, and previous pain, hospitalization and surgery on children’s ( N = 60) perceptions of anxiety, pain intensity, quality of pain and sleep, and oral intake. The relationship between postoperative pain and anxiety was also examined. Using a diary, three days of data were collected. Descriptive statistics, Pearson correlation coefficient, and a mixed linear regression model were used for analysis. Children’s tonsillectomy experiences and outcomes were affected by time, previous experience, age, and anxiety. Moderate correlations were found between level of anxiety and pain intensity. These findings provide clinicians with additional knowledge to guide their perioperative practice and care of children.
Exploring three-year-old children in a primary child health care situation
Authors: Harder Maria , Christensson Kyllike , Söderbäck Maja
Published: October 2009

In the Swedish Primary Child Health Care (PCHC) children participate in regular health visits. In these visits children as actors demonstrate their subjective maturity through bodily and verbal expressions. The aim of this study was to explore three-year-old children’s expressions when they take part as actors in a PCHC situation. An explorative design with a hermeneutic approach and video observations was used. Twenty-nine children participated. The findings exhibit a variation of expressions in the situation conceptualized as actions in a progression of states: from a state of getting ready to a state of being ready and further to a state where the child strengthens their own self. This progression is dynamic and coloured with the states of not being ready or of being adverse. The conceptualization of children’s expressions can contribute towards encouraging nurses’ sensitivity when inviting and guiding children in PCHC situations.
‘They wouldn’t know how it feels . . .’: characteristics of quality care from young people’s perspectives: a participatory research project
Authors: Moules Tina
Published: October 2009

Literature suggests there is a need to hear from children themselves about the quality of healthcare they receive and, although their views are increasingly sought, little is known about children’s definitions of ‘high or low quality care’. This article reports on a participatory, qualitative study that set out to explore with children and young people whether they could be involved in monitoring the quality of hospital care. Nine young people played an active role in the research process, collecting data from an additional 129 participants aged between 9 and 14. Five characteristics of quality care were identified: ‘technical expertise’, ‘friendly staff ’, ‘respect’, ‘choice’ and ‘explanations’.
Lost and Mastermind Narration
Authors: Clarke M.J.
Published: October 2009

ABC’s Lost is indicative of a recent trend in television programming that exploits seriality, information multiplicity and real virtuality. While these aesthetic innovations have arguably facilitated the franchising of this and other programs, it has also created several textual problems around the issues of canon, authority and narration. In this article, I illustrate how Lost uses the strategies of what I call mastermind narration to rearticulate this imperiled textual authority. The strategies of this tendency include the use of repeated subject matter, particularly confidence tricks, and the patterning of textual form, particularly through shifting the narrational valence of series flashbacks.
Inducing the tryptophan catabolic pathway, indoleamine 2,3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality
Authors: Jasperson Lisa K. , Bucher Christoph , Panoskaltsis-Mortari Angela , Mellor Andrew L. , Munn David H. , Blazar Bruce R.
Published: October 2009

During graft-versus-host disease (GVHD), donor T cells become activated and migrate to tissue sites. Previously, we demonstrated a crucial role for the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) in GVHD regulation. Here, we show that upon arrival in the colon, activated donor T cells produced interferon-γ that up-regulated IDO, causing T-cell anergy and apoptosis. IDO induces GCN2 kinase, up-regulating a T-cell stress response implicated in IDO immunosuppression. Donor T cells did not require GCN2 kinase to respond to IDO, suggesting toxic IDO metabolites, and not tryptophan depletion, were responsible for suppression. When exogenous metabolites were administered, GVHD lethality was reduced. To determine whether IDO could be induced before transplantation for enhanced GVHD suppression, we first determined whether antigen-presenting cells (APCs) or epithelial cells were primarily responsible for IDO expression and subsequent GVHD suppression. Recipients with wild-type versus IDO−/− APCs had increased survival, regardless of epithelial-cell expression of IDO, suggesting that APCs were suitable targets for inducing IDO. Administration of an agonist to toll-like receptor-7/8, a receptor expressed primarily on APCs, induced IDO and reduced injury in the colon and ameliorated lethality. We conclude that IDO up-regulation may have therapeutic potential for preventing GVHD in the clinic.
Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain
Authors: Lin Yi-Ruu , Chen Hwei-Hsien , Lin Yu-Chin , Ko Chien-Hsin , Chan Ming-Huan
Published: October 2009

The antinociceptive effects of honokiol and magnolol, two major bioactive constituents of the bark ofMagnolia officinalis, were investigated on animal paw licking responses and thermal hyperalgesia induced by glutamate receptor agonists including glutamate, N-methyl-D-aspartate (NMDA), and metabotropic glutamate 5 receptor (mGluR5) activator (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as inflammatory mediators such as substance P and prostaglandin E2(PGE2) in mice. The actions of honokiol and magnolol on glutamate-induced c-Fos expression in the spinal cord dorsal horn were also examined. Our data showed that honokiol and magnolol blocked glutamate-, substance P- and PGE2-induced inflammatory pain with similar potency and efficacy. Consistently, honokiol and magnolol significantly decreased glutamate-induced c-Fos protein expression in superficial (I-II) laminae of the L4-L5 lumbar dorsal horn. However, honokiol was more selective than magnolol for inhibition of NMDA-induced licking behavioral and thermal hyperalgesia. In contrast, magnolol was more potent to block CHPG-mediated thermal hyperalgesia. These results demonstrate that honokiol and magnolol effectively decreased the inflammatory pain. Furthermore, their different potency on inhibition of nociception provoked by NMDA receptor and mGluR5 activation should be considered.
Differential effects of cytokines and corticosteroids on Toll-like receptor 2 expression and activity in human airway epithelia
Authors: Winder Audra A , Wohlford-Lenane Christine , Scheetz Todd E , Nardy Brie N , Manzel Lori J , Look Dwight C , McCray Paul B
Published: October 2009

Background

The recognition of microbial molecular patterns via Toll-like receptors (TLRs) is critical for mucosal defenses.

Methods

Using well-differentiated primary cultures of human airway epithelia, we investigated the effects of exposure of the cells to cytokines (TNF-α and IFN-γ) and dexamethasone (dex) on responsiveness to the TLR2/TLR1 ligand Pam3CSK4. Production of IL-8, CCL20, and airway surface liquid antimicrobial activity were used as endpoints.

Results

Microarray expression profiling in human airway epithelia revealed that first response cytokines markedly induced TLR2 expression. Real-time PCR confirmed that cytokines (TNF-α and IFN-γ), dexamethasone (dex), or cytokines + dex increased TLR2 mRNA abundance. A synergistic increase was seen with cytokines + dex. To assess TLR2 function, epithelia pre-treated with cytokines ± dex were exposed to the TLR2/TLR1 ligand Pam3CSK4 for 24 hours. While cells pre-treated with cytokines alone exhibited significantly enhanced IL-8 and CCL20 secretion following Pam3CSK4, mean IL-8 and CCL20 release decreased in Pam3CSK4 stimulated cells following cytokines + dex pre-treatment. This marked increase in inflammatory gene expression seen after treatment with cytokines followed by the TLR2 ligand did not correlate well with NF-κB, Stat1, or p38 MAP kinase pathway activation. Cytokines also enhanced TLR2 agonist-induced beta-defensin 2 mRNA expression and increased the antimicrobial activity of airway surface liquid. Dex blocked these effects.

Conclusion

While dex treatment enhanced TLR2 expression, co-administration of dex with cytokines inhibited airway epithelial cell responsiveness to TLR2/TLR1 ligand over cytokines alone. Enhanced functional TLR2 expression following exposure to TNF-α and IFN-γ may serve as a dynamic means to amplify epithelial innate immune responses during infectious or inflammatory pulmonary diseases.
Mapping of protein phosphatase-6 association with its SAPS domain regulatory subunit using a model of helical repeats
Authors: Guergnon Julien , Derewenda Urszula , Edelson Jessica R , Brautigan David L
Published: October 2009

Background

Helical repeat motifs are common among regulatory subunits for type-1 and type-2A protein Ser/Thr phosphatases. Yeast Sit4 is a distinctive type-2A phosphatase that has dedicated regulatory subunits named Sit4-Associated Proteins (SAPS). These subunits are conserved, and three human SAPS-related proteins are known to associate with PP6 phosphatase, the Sit4 human homologue.

Results

Here we show that endogenous SAPS subunit PP6R3 co-precipitates half of PP6 in cell extracts, and the SAPS region of PP6R3 is sufficient for binding PP6. The SAPS domain of recombinant GST-PP6R3 is relatively resistant to trypsin despite having many K and R residues, and the purified SAPS domain (residues 1-513) has a circular dichroic spectrum indicative of mostly alpha helical structure. We used sequence alignments and 3D-jury methods to develop alternative models for the SAPS domain, based on available structures of other helical repeat proteins. The models were used to select sites for charge-reversal substitutions in the SAPS domain of PP6R3 that were tested by co-precipitation of endogenous PP6c with FLAG-tagged PP6R3 from mammalian cells. Mutations that reduced binding with PP6 suggest that SAPS adopts a helical repeat similar to the structure of p115 golgin, but distinct from the PP2A-A subunit. These mutations did not cause perturbations in overall PP6R3 conformation, evidenced by no change in kinetics or preferential cleavage by chymotrypsin.

Conclusion

The conserved SAPS domain in PP6R3 forms helical repeats similar to those in golgin p115 and negatively charged residues in interhelical loops are used to associate specifically with PP6. The results advance understanding of how distinctive helical repeat subunits uniquely distribute and differentially regulate closely related Ser/Thr phosphatases.
Clustering of protein domains for functional and evolutionary studies
Authors: Goldstein Pavle , Zucko Jurica , Vujaklija Dušica , Kriško Anita , Hranueli Daslav , Long Paul F , Etchebest Catherine , Basrak Bojan , Cullum John
Published: October 2009

Background

The number of protein family members defined by DNA sequencing is usually much larger than those characterised experimentally. This paper describes a method to divide protein families into subtypes purely on sequence criteria. Comparison with experimental data allows an independent test of the quality of the clustering.

Results

An evolutionary split statistic is calculated for each column in a protein multiple sequence alignment; the statistic has a larger value when a column is better described by an evolutionary model that assumes clustering around two or more amino acids rather than a single amino acid. The user selects columns (typically the top ranked columns) to construct a motif. The motif is used to divide the family into subtypes using a stochastic optimization procedure related to the deterministic annealing EM algorithm (DAEM), which yields a specificity score showing how well each family member is assigned to a subtype. The clustering obtained is not strongly dependent on the number of amino acids chosen for the motif. The robustness of this method was demonstrated using six well characterized protein families: nucleotidyl cyclase, protein kinase, dehydrogenase, two polyketide synthase domains and small heat shock proteins. Phylogenetic trees did not allow accurate clustering for three of the six families.

Conclusion

The method clustered the families into functional subtypes with an accuracy of 90 to 100%. False assignments usually had a low specificity score.
Integrating functional genomics data using maximum likelihood based simultaneous component analysis
Authors: van den Berg Robert A , Van Mechelen Iven , Wilderjans Tom F , Van Deun Katrijn , Kiers Henk AL , Smilde Age K
Published: October 2009

Background

In contemporary biology, complex biological processes are increasingly studied by collecting and analyzing measurements of the same entities that are collected with different analytical platforms. Such data comprise a number of data blocks that are coupled via a common mode. The goal of collecting this type of data is to discover biological mechanisms that underlie the behavior of the variables in the different data blocks. The simultaneous component analysis (SCA) family of data analysis methods is suited for this task. However, a SCA may be hampered by the data blocks being subjected to different amounts of measurement error, or noise. To unveil the true mechanisms underlying the data, it could be fruitful to take noise heterogeneity into consideration in the data analysis. Maximum likelihood based SCA (MxLSCA-P) was developed for this purpose. In a previous simulation study it outperformed normal SCA-P. This previous study, however, did not mimic in many respects typical functional genomics data sets, such as, data blocks coupled via the experimental mode, more variables than experimental units, and medium to high correlations between variables. Here, we present a new simulation study in which the usefulness of MxLSCA-P compared to ordinary SCA-P is evaluated within a typical functional genomics setting. Subsequently, the performance of the two methods is evaluated by analysis of a real life Escherichia coli metabolomics data set.

Results

In the simulation study, MxLSCA-P outperforms SCA-P in terms of recovery of the true underlying scores of the common mode and of the true values underlying the data entries. MxLSCA-P further performed especially better when the simulated data blocks were subject to different noise levels. In the analysis of an E. coli metabolomics data set, MxLSCA-P provided a slightly better and more consistent interpretation.

Conclusion

MxLSCA-P is a promising addition to the SCA family. The analysis of coupled functional genomics data blocks could benefit from its ability to take different noise levels per data block into consideration and improve the recovery of the true patterns underlying the data. Moreover, the maximum likelihood based approach underlying MxLSCA-P could be extended to custom-made solutions to specific problems encountered.
In silico saturation mutagenesis and docking screening for the analysis of protein-ligand interaction: the Endothelial Protein C Receptor case study
Authors: Chiappori Federica , D'Ursi Pasqualina , Merelli Ivan , Milanesi Luciano , Rovida Ermanna
Published: October 2009

Background

The design of mutants in protein functional regions, such as the ligand binding sites, is a powerful approach to recognize the determinants of specific protein activities in cellular pathways. For an exhaustive analysis of selected positions of protein structure large scale mutagenesis techniques are often employed, with laborious and time consuming experimental set-up. 'In silico' mutagenesis and screening simulation represents a valid alternative to laboratory methods to drive the 'in vivo' testing toward more focused objectives.

Results

We present here a high performance computational procedure for large-scale mutant modelling and subsequent evaluation of the effect on ligand binding affinity. The mutagenesis was performed with a 'saturation' approach, where all 20 natural amino acids were tested in positions involved in ligand binding sites. Each modelled mutant was subjected to molecular docking simulation and stability evaluation. The simulated protein-ligand complexes were screened for their impairment of binding ability based on change of calculated Ki compared to the wild-type.

An example of application to the Endothelial Protein C Receptor residues involved in lipid binding is reported.

Conclusion

The computational pipeline presented in this work is a useful tool for the design of structurally stable mutants with altered affinity for ligand binding, considerably reducing the number of mutants to be experimentally tested. The saturation mutagenesis procedure does not require previous knowledge of functional role of the residues involved and allows extensive exploration of all possible substitutions and their pairwise combinations. Mutants are screened by docking simulation and stability evaluation followed by a rationally driven selection of those presenting the required characteristics. The method can be employed in molecular recognition studies and as a preliminary approach to select models for experimental testing.
Karyopherin binding interactions and nuclear import mechanism of nuclear pore complex protein Tpr
Authors: Ben-Efraim Iris , Frosst Phyllis D , Gerace Larry
Published: October 2009

Background

Tpr is a large protein with an extended coiled-coil domain that is localized within the nuclear basket of the nuclear pore complex. Previous studies [1] involving antibody microinjection into mammalian cells suggested a role for Tpr in nuclear export of proteins via the CRM1 export receptor. In addition, Tpr was found to co-immunoprecipitate with importins α and β from Xenopus laevis egg extracts [2], although the function of this is unresolved. Yeast Mlp1p and Mlp2p, which are homologous to vertebrate Tpr, have been implicated in mRNA surveillance to retain unspliced mRNAs in the nucleus[3, 4]. To augment an understanding of the role of Tpr in nucleocytoplasmic trafficking, we explored the interactions of recombinant Tpr with the karyopherins CRM1, importin β and importin α by solid phase binding assays. We also investigated the conditions required for nuclear import of Tpr using an in vitro assay.

Results

We found that Tpr binds strongly and specifically to importin α, importin β, and a CRM1 containing trimeric export complex, and that the binding sites for importins α and β are distinct. We also determined that the nuclear import of Tpr is dependent on cytosolic factors and energy and is efficiently mediated by the importin α/β import pathway.

Conclusion

Based on the binding and nuclear import assays, we propose that Tpr is imported into the nucleus by the importin α/β heterodimer. In addition, we suggest that Tpr can serve as a nucleoporin binding site for importin β during import of importin β cargo complexes and/or importin β recycling. Our finding that Tpr bound preferentially to CRM1 in an export complex strengthens the notion that Tpr is involved in protein export.
Transposon-mediated BAC transgenesis in zebrafish and mice
Authors: Suster Maximiliano L , Sumiyama Kenta , Kawakami Koichi
Published: October 2009

Background

Bacterial artificial chromosomes (BACs) are among the most widely used tools for studies of gene regulation and function in model vertebrates, yet methods for predictable delivery of BAC transgenes to the genome are currently limited. This is because BAC transgenes are usually microinjected as naked DNA into fertilized eggs and are known to integrate as multi-copy concatamers in the genome. Although conventional methods for BAC transgenesis have been very fruitful, complementary methods for generating single copy BAC integrations would be desirable for many applications.

Results

We took advantage of the precise cut-and-paste behavior of a natural transposon, Tol2, to develop a new method for BAC transgenesis. In this new method, the minimal sequences of the Tol2 transposon were used to deliver precisely single copies of a ~70 kb BAC transgene to the zebrafish and mouse genomes. We mapped the BAC insertion sites in the genome by standard PCR methods and confirmed transposase-mediated integrations.

Conclusion

The Tol2 transposon has a surprisingly large cargo capacity that can be harnessed for BAC transgenesis. The precise delivery of single-copy BAC transgenes by Tol2 represents a useful complement to conventional BAC transgenesis, and could aid greatly in the production of transgenic fish and mice for genomics projects, especially those in which single-copy integrations are desired.
Outer membrane vesicle-mediated release of cytolethal distending toxin (CDT) from Campylobacter jejuni
Authors: Lindmark Barbro , Rompikuntal Pramod Kumar , Vaitkevicius Karolis , Song Tianyan , Mizunoe Yoshimitsu , Uhlin Bernt Eric , Guerry Patricia , Wai Sun Nyunt
Published: October 2009

Background

Background: Cytolethal distending toxin (CDT) is one of the well-characterized virulence factors of Campylobacter jejuni, but it is unknown how CDT becomes surface-exposed or is released from the bacterium to the surrounding environment.

Results

Our data suggest that CDT is secreted to the bacterial culture supernatant via outer membrane vesicles (OMVs) released from the bacteria. All three subunits (the CdtA, CdtB, and CdtC proteins) were detected by immunogold labeling and electron microscopy of OMVs. Subcellular fractionation of the bacteria indicated that, apart from the majority of CDT detected in the cytoplasmic compartment, appreciable amounts (20-50%) of the cellular pool of CDT proteins were present in the periplasmic compartment. In the bacterial culture supernatant, we found that a majority of the extracellular CDT was tightly associated with the OMVs. Isolated OMVs could exert the cell distending effects typical of CDT on a human intestinal cell line, indicating that CDT is present there in a biologically active form.

Conclusion

Our results strongly suggest that the release of outer membrane vesicles is functioning as a route of C. jejuni to deliver all the subunits of CDT toxin (CdtA, CdtB, and CdtC) to the surrounding environment, including infected host tissue.