bluuebunny/crossref_metadata_2025 huggingface dataset:
Loosing soft power in hard places
Authors: Munslow Barry , O'Dempsey Tim
Published: January 2009

The US choice of a misdirected target of priority concern, a ‘War on Terror’, combined with the use of hard power to the absolute detriment of soft power has undermined the enlightenment values that had begun to flourish in the form of humanitarian policies, values and laws which could have informed international cooperation and development in the twenty-first century. The US-led invasion of Iraq in 2003 has had serious implications for humanitarianism worldwide, has provided a huge propaganda victory to Islamic extremists, and has diverted international attention and resources from major humanitarian emergencies elsewhere and from today's most significant threat to human survival, global climate change.
‘It's like talking to a brick wall’
Authors: Whittall Jonathan
Published: January 2009

For the purpose of this article, humanitarian diplomacy is defined as: the use of International Law and the humanitarian imperative as complimentary levers to facilitate the delivery of assistance or to promote the protection of civilians in a complex political emergency.

Based on field research in the occupied Palestinian territory in 2007, this article demonstrates that the external reality of a US global superpower overly reliant on hard power, combined with its strategic alliance with Israel in the Middle East, creates an operating environment that severely constrains the use of humanitarian diplomacy. Whilst United Nations (UN) agencies implement technically sound interventions, the political realities prevent the effective use of International Law.

The UN field staff are evoking Palestinian's humanitarian needs as a lever to promote protection, but this is fundamentally missing the point. The situation in the West Bank is a human rights issue – borne from a political crisis. The protection of Palestinians is undermined by an aversion to the use of International Law because of the political realities of an unchallenged occupation.
Treating AIDS in complex emergencies
Authors: Ford Nathan
Published: January 2009

Human Immunodefficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is directly responsible for increased mortality in many humanitarian crises and can exacerbate vulnerability linked to food insecurity, loss of livelihood and disrupted coping mechanisms. However, the need to provide antiretroviral therapy as part of a comprehensive response to HIV/AIDS, in conflict and emergency settings, is not universally accepted. Established humanitarian organizations have, until recently, raised logistical, technical and ethical concerns about providing treatment in conflict and post-conflict settings, while interagency guidelines continue to recommend against providing antiretrovirals in post-disaster settings. There is mounting evidence that this viewpoint needs to be revised.
Fair training
Authors: O'Dempsey Tim
Published: January 2009

Major catastrophes appear to be inevitable given the current demographic transition, the growth of mega-cities in disaster hotspots, the predicted effects of global climate change, and the crucial relationship between natural disasters and complex political emergencies. Disaster prevention, preparedness and contingency planning will be effective only if trained personnel are available to develop these plans and implement them in a timely manner. Workforce migration, driven by poverty, insecurity and lack of opportunity, creates a leadership and skills vacuum that further increases the vulnerability of those who remain. Sustainable solutions to the problems of disasters and development will only be achieved when poor people have local access to Fair Training.
Visual repairables: analysing the work of repair in human–computer interaction
Authors: Greiffenhagen Christian , Watson Rod
Published: January 2009

This article reports some (video-recorded) instances of `visual culture' in action, namely the use of a new software tool designed for the visualization of scenes from Shakespeare's Macbeth in a classroom context. By considering whether or how far conversation analysis (CA) can be extended from natural conversation to cases of collaborative work in front of a computer, the article addresses the methodological question of how to study instances of visual communication. We take as an exemplar the phenomenon of remedial action and discuss how Schegloff, Jefferson and Sacks's (1977) canonical study of repair in ordinary conversation can be used to highlight aspects of `visual repair' (the identification and remedying of items on the screen). Our attempts to apply the original CA model of repair of ordinary conversation highlight the differences of this setting, which constitutes an example of collaborative work.
Layout as punctuation of semiosis: some examples from Israeli schoolbooks
Authors: Peled-Elhanan Nurit
Published: January 2009

This article examines the function of layout in the representation of the Palestinian—Israeli conflict in three history textbooks used in Israeli schools. The analysis elaborates on two concepts of Kress and Van Leeuwen — `ideological layout' and `punctuation of semiosis'. The author argues that layout may `punctuate' semiosis in two different senses: first, in the sense of `bringing (conventional—official) semiosis to a temporary standstill in textual form'; and, second, in the sense of `piercing a hole' in the conventional or official semiosis it presents, and thereby criticizing it. In both cases, layout creates new complex signs that either support or contradict the verbal and visual texts it presents.

This study suggests that layout analysis may help answer larger questions concerning `the transformation of social practices into discourses about social practices in specific institutional contexts' (Van Leeuwen, 1996). The discussion of the means by which these punctuations are achieved and the messages they convey is followed by reflections upon the difficulties students and teachers may have in reading such multimodal texts.
A fatal case of airway obstruction by an organic one-way valve
Authors: Bresci F , Di Paolo M , Martelli M , De Simone L , Giunta F , Ambrosino N
Published: January 2009

We report a fatal case of airway obstruction. A tracheostomized, spontaneously breathing 39-year-old man developed dyspnea, cardiac, and respiratory arrest after tracheal cannula replacement. Inspection of the cannula showed a blood clot obstructing the tube. Autopsy showed pink foam in the trachea, pulmonary hyperinflation, and congested lung parenchyma. Histological examination showed acute pulmonary emphysema without any sign of blood inhalation. The probable pathophysiological mechanism is a clot creating a one-way valve allowing inspiration but not expiration, resulting in dyspnea and pulmonary hyperinflation.
Saber-sheath trachea in a patient with bronchiolitis obliterans syndrome after lung transplantation
Authors: Hayes D , Ballard HO
Published: January 2009

Chronic rejection remains a major source of morbidity and mortality following lung transplantation. The clinical characteristics of chronic rejection involves bronchiolitis obliterans syndrome (BOS), which leads to progressive airway obstruction. Changes in intrathoracic tracheal dimensions and shape are commonly present in the setting of airway obstruction, leading to the narrowing of the intrathoracic trachea in the coronal plane with anteroposterior lengthening characteristic of the saber-sheath trachea deformity. We present a 64-year-old man who underwent left lung transplantation for idiopathic pulmonary fibrosis who later developed saber-sheath trachea as a result of chronic airway obstruction due to BOS.
Mapping a Message for Faith Leaders: Encouraging Community Health Promotion With Local Health Data
Authors: Kruger Daniel J. , Lewis Yvonne , Schlemmer Erin
Published: January 2009

This study reports the use of a community-based health survey to share local health information with faith leaders. Geographical information systems software identified survey respondents within 2 km (1.25 miles) of places of worship. Results were tabulated for the community surrounding each place of worship and were compared with city- and county-level data. Faith leaders were presented with community-specific reports describing the health attributes of residents who lived in the surrounding area, in order to assist with the identification issues of concern and opportunities to develop health ministries to address these issues. Faith leaders were encouraged to share this information with members of their faith community and develop means of obtaining additional information on the people of interest. We believe that engaging faith leaders with neighborhood-specific health information will be critical in providing an understanding of the importance of their voice in improving health outcomes of their faith community, the surrounding neighborhood, and the community at large. Our goal is to empower faith leaders to understand personal and community health issues and to act as a conduit for health-related information and health promotion at a local level. Church health teams developed an HIV and sexually transmitted infection prevention program for African American adolescents and young adults.
Physical Activity Promotion Among Underserved Adolescents: “Make It Fun, Easy, and Popular”
Authors: Louise Bush Paula , Laberge Suzanne , Laforest Sophie
Published: January 2009

There is a paucity of studies regarding noncurricular physical activity promotion interventions among adolescents, and even less such research pertaining to underserved youth. This article describes the development and implementation of a noncurricular, school-based physical activity promotion program designed for a multiethnic, underserved population of adolescents. The program’s impact on leisure-time physical activity (LTPA) and on physical activity enjoyment (PAE) is also presented. The 16-week program, named FunAction, utilizes social marketing principles. Control (n = 90) and intervention (n = 131) students are assessed pre- and postintervention for levels of LTPA and PAE. Results indicate that although the program did not contribute to an increase in LTPA or PAE among intervention group students, participation in the program was elevated. This study offers preliminary evidence that noncurricular physical activity promotion programs that apply social marketing principles can be effective in engaging multiethnic, underserved adolescents in physical activity.
Estimating Household Water Use: A Comparison of Diary, Prompted Recall, and Free Recall Methods
Authors: Wutich Amber
Published: January 2009

Studies of household water use are often based on retrospective behavioral reports, which are vulnerable to threats to informant accuracy. This article compares three methods for collecting household water use data: a diary, prompted recall, and free recall. The analyses are based on data from seventy-two randomly selected households in Cochabamba, Bolivia. Per capita water use estimates based on the three methods were significantly different. When compared against known parameters, the diary provided the most accurate estimate of household water use. The prompted recall method yielded similar results to the diary method on hygienic and food preparation tasks, but there were significant differences on household cleaning tasks. The free recall method significantly underestimated water use. There were not significant differences in water use assessments within households, but there was variation in misestimation across households. The article discusses which participants (e.g., heads of less water-consumptive households) provided more reliable water use estimates.
Identification and Exploration of Herb-Drug Combinations Used By Cancer Patients
Authors: Engdal Silje , Klepp Olbjørn , Nilsen Odd Georg
Published: January 2009

Introduction: This survey aims to identify herb-chemotherapeutic drug combinations in a defined group of cancer patients and to explore possible clinical consequences of these combinations. Methods: Herb-chemotherapeutic drug combinations were identified among adult cancer patients, and clinical consequences of the combinations were explored by literature searches in medical databases on possible mutual effects on similar cytochrome P-450 metabolising enzymes (CYPs) and/or the P-glycoprotein (P-gp) transporter. Results: Among 42 cancer patients using herbal remedies concurrently with chemotherapy, 136 two-agent herb-drug combinations were registered and 47 different potential herb-drug interactions were identified on the level of CYP metabolism and P-gp transport in vitro. Garlic, ginger, green tea and noni juice were the herbal remedies most frequently used in such combinations. For 48 % of the herbal remedies identified no literature data exist on their interaction potentials. Clinical studies were available for four herbal remedies only. Minor clinical potential for CYP interactions in humans was indicated for green tea and Echinacea. P-gp interactions were only investigated for garlic, which showed a significant interaction potential both in vivo and in vitro. Conclusion: The large number of in vitro potential herb-drug interactions identified urge for more clinical pharmacokinetic interaction studies in humans.
Trastuzumab and Doxorubicin-Related Cardiotoxicity and the Cardioprotective Role of Exercise
Authors: Wonders Karen Y. , Reigle Beverly S.
Published: January 2009

Women diagnosed with breast cancer typically undergo a multimodal approach to treating their disease. The treatments used often result in sequelae such as fatigue, hair loss, nausea and vomiting, and functional impairment. Many of these sequelae can be controlled or eliminated with pharmacological, physical, or social interventions. However, 2 effective cytotoxic agents, doxorubicin and trastuzumab, are associated with a potentially life-threatening sequela, cardiotoxicity. Currently, these agents are dosage and duration limited to circumvent cardiac damage. Exercise prior to and during the administration of these agents is emerging as a possible cardioprotective intervention based on the findings of animal model studies. Incorporating exercise into the breast cancer treatment trajectory may eliminate the dosage and duration restrictions of these antineoplastic agents and ultimately affect survival and quality of life. The authors present the pharmacological mechanism for each agent and the exciting results of animal model studies that lay the groundwork for future clinical trials.
Milk-Based Nutritional Supplements in Conjunction With Lifestyle Intervention in Overweight Adolescents
Authors: Apovian Caroline , Bigornia Sherman , Cullum-Dugan Diana , Schoonmaker Chris , Radziejowska Joanna , Phipps Jenna , Gokce Noyan , Istfan Nawfal , Meyers Alan , Lenders Carine
Published: January 2009

There are limited data on successful weight management approaches among adolescents from underserved communities. The primary aim of this study was to obtain preliminary data on the efficacy, safety, and acceptability of a lifestyle intervention with milk-based supplements among adolescents from underserved communities. The secondary aims of this study were to assess change in adiposity indices and metabolic indices and to measure compliance. The authors conducted a 12-week open-labeled lifestyle intervention. Adolescents were taught a structured meal plan, including the use of 2 milk-based supplements daily, and participated in weekly lifestyle counseling. Overweight was defined as a body mass index >85th percentile. Percent total body fat was estimated using bioelectric impedance. Fasting blood samples were used to measure insulin indices and other biochemical safety tests. The sample consisted of 40 adolescents (70% girls, 83% minority). Although there was no significant change in body mass index (median [Q1, Q3]; –0.10 [–0.91, 0.61] kg/m2, P = .26), participants showed a decrease in body mass index z score (–0.03 [-0.08, 0.01] SD, P = .01]), weight z score (–0.04 [–0.11, 0.02] SD, P = .001), and percent total body fat (–1.20 [–2.55, –0.12]%, P = .0001). No new onset of type 2 diabetes mellitus was reported, and plasma vitamin D increased ( P –.01). Consumption of milk-based drinks increased from a median of 4.5 to 13.5 servings per week, whereas sugary beverages decreased from 8.0 to 3.8 servings per week. A lifestyle intervention that includes milk-based supplements may safely improve some adiposity indices and decrease intake of sugary beverages among overweight adolescents from underserved areas.
Quantifying the development of the peripheral naive CD4+ T-cell pool in humans
Authors: Bains Iren , Antia Rustom , Callard Robin , Yates Andrew J.
Published: January 2009

What are the rules that govern a naive T cell's prospects for survival or division after export from the thymus into the periphery? To help address these questions, we combine data from existing studies with robust mathematical models to estimate the absolute contributions of thymopoiesis, peripheral division, and loss or differentiation to the human naive CD4+ T-cell pool between the ages of 0 and 20 years. Despite their decline in frequency in the blood, total body numbers of naive CD4+ T cells increase throughout childhood and early adulthood. Our analysis shows that postthymic proliferation contributes more than double the number of cells entering the pool each day from the thymus. This ratio is preserved with age; as the thymus involutes, the average time between naive T-cell divisions in the periphery lengthens. We also show that the expected residence time of naive T cells increases with time. The naive CD4+ T-cell population thus becomes progressively less dynamic with age. Together with other studies, our results suggest a complex picture of naive T-cell homeostasis in which population size, time since export from the thymus, or time since the last division can influence a cell's prospects for survival or further divisions.
Dendritic cell homeostasis
Authors: Merad Miriam , Manz Markus G.
Published: January 2009

Dendritic cells (DCs) are a heterogeneous fraction of rare hematopoietic cells that coevolved with the formation of the adaptive immune system. DCs efficiently process and present antigen, move from sites of antigen uptake to sites of cellular interactions, and are critical in the initiation of immune responses as well as in the maintenance of self-tolerance. DCs are distributed throughout the body and are enriched in lymphoid organs and environmental contact sites. Steady-state DC half-lives account for days to up to a few weeks, and they need to be replaced via proliferating hematopoietic progenitors, monocytes, or tissue resident cells. In this review, we integrate recent knowledge on DC progenitors, cytokines, and transcription factor usage to an emerging concept of in vivo DC homeostasis in steady-state and inflammatory conditions. We furthermore highlight how knowledge of these maintenance mechanisms might impact on understanding of DC malignancies as well as posttransplant immune reactions and their respective therapies.
Prediction of protein-protein interaction types using association rule based classification
Authors: Park Sung Hee , Reyes José A , Gilbert David R , Kim Ji Woong , Kim Sangsoo
Published: January 2009

Background

Protein-protein interactions (PPI) can be classified according to their characteristics into, for example obligate or transient interactions. The identification and characterization of these PPI types may help in the functional annotation of new protein complexes and in the prediction of protein interaction partners by knowledge driven approaches.

Results

This work addresses pattern discovery of the interaction sites for four different interaction types to characterize and uses them for the prediction of PPI types employing Association Rule Based Classification (ARBC) which includes association rule generation and posterior classification. We incorporated domain information from protein complexes in SCOP proteins and identified 354 domain-interaction sites. 14 interface properties were calculated from amino acid and secondary structure composition and then used to generate a set of association rules characterizing these domain-interaction sites employing the APRIORI algorithm. Our results regarding the classification of PPI types based on a set of discovered association rules shows that the discriminative ability of association rules can significantly impact on the prediction power of classification models. We also showed that the accuracy of the classification can be improved through the use of structural domain information and also the use of secondary structure content.

Conclusion

The advantage of our approach is that we can extract biologically significant information from the interpretation of the discovered association rules in terms of understandability and interpretability of rules. A web application based on our method can be found at http://bioinfo.ssu.ac.kr/~shpark/picasso/
Bioelectrical impedance phase angle in clinical practice: implications for prognosis in stage IIIB and IV non-small cell lung cancer
Authors: Gupta Digant , Lammersfeld Carolyn A , Vashi Pankaj G , King Jessica , Dahlk Sadie L , Grutsch James F , Lis Christopher G
Published: January 2009

Background

A frequent manifestation of advanced lung cancer is malnutrition, timely identification and treatment of which can lead to improved patient outcomes. Bioelectrical impedance analysis (BIA) is an easy-to-use and non-invasive technique to evaluate changes in body composition and nutritional status. We investigated the prognostic role of BIA-derived phase angle in advanced non-small cell lung cancer (NSCLC).

Methods

A case series of 165 stages IIIB and IV NSCLC patients treated at our center. The Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle, independent of stage at diagnosis and prior treatment history.

Results

93 were males and 72 females. 61 had stage IIIB disease at diagnosis while 104 had stage IV. The median phase angle was 5.3 degrees (range = 2.9 – 8). Patients with phase angle <= 5.3 had a median survival of 7.6 months (95% CI: 4.7 to 9.5; n = 81), while those with > 5.3 had 12.4 months (95% CI: 10.5 to 18.7; n = 84); (p = 0.02). After adjusting for age, stage at diagnosis and prior treatment history we found that every one degree increase in phase angle was associated with a relative risk of 0.79 (95% CI: 0.64 to 0.97, P = 0.02).

Conclusion

We found BIA-derived phase angle to be an independent prognostic indicator in patients with stage IIIB and IV NSCLC. Nutritional interventions targeted at improving phase angle could potentially lead to an improved survival in patients with advanced NSCLC.
Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment
Authors: Node Koichi , Inoue Teruo , Boyko Valentin , Goldberg Ilan , Fisman Enrique Z , Adler Yehuda , Schwammenthal Ehud , Matas Zipora , Behar Solomon , Tenenbaum Alexander
Published: January 2009

Background

The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment.

Methods

Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up.

Results

During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3).

Conclusion

Long-term treatment by bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment.
Implication of granulocyte-macrophage colony-stimulating factor induced neutrophil gelatinase-associated lipocalin in pathogenesis of rheumatoid arthritis revealed by proteome analysis
Authors: Katano Masayoshi , Okamoto Kazuki , Arito Mitsumi , Kawakami Yuki , Kurokawa Manae S , Suematsu Naoya , Shimada Sonoko , Nakamura Hiroshi , Xiang Yang , Masuko Kayo , Nishioka Kusuki , Yudoh Kazuo , Kato Tomohiro
Published: January 2009

Introduction

In rheumatoid arthritis (RA), synovial fluid (SF) contains a large number of neutrophils that contribute to the inflammation and destruction of the joints. The SF also contains granulocyte-macrophage colony-stimulating factor (GM-CSF), which sustains viability of neutrophils and activates their functions. Using proteomic surveillance, we here tried to elucidate the effects of GM-CSF on neutrophils.

Methods

Neutrophils stimulated by GM-CSF were divided into four subcellular fractions: cytosol, membrane/organelle, nuclei, and cytoskeleton. Then, proteins were extracted from each fraction and digested by trypsin. The produced peptides were detected using matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry (MALDI-TOF MS).

Results

We detected 33 peptide peaks whose expression was upregulated by more than 2.5-fold in GM-CSF stimulated neutrophils and identified 11 proteins out of the 33 peptides using MALDI-TOF/TOF MS analysis and protein database searches. One of the identified proteins was neutrophil gelatinase-associated lipocalin (NGAL). We confirmed that the level of NGAL in SF was significantly higher in patients with RA than in those with osteoarthritis. We next addressed possible roles of the increased NGAL in RA. We analysed proteome alteration of synoviocytes from patients with RA by treatment with NGAL in vitro. We found that, out of the detected protein spots (approximately 3,600 protein spots), the intensity of 21 protein spots increased by more than 1.5-fold and the intensity of 10 protein spots decreased by less than 1 to 1.5-fold as a result of the NGAL treatment. Among the 21 increased protein spots, we identified 9 proteins including transitional endoplasmic reticulum ATPase (TERA), cathepsin D, and transglutaminase 2 (TG2), which increased to 4.8-fold, 1.5-fold and 1.6-fold, respectively. Two-dimensional electrophoresis followed by western blot analysis confirmed the upregulation of TERA by the NGAL treatment and, moreover, the western blot analysis showed that the NGAL treatment changed the protein spots caused by post-translational modification of TERA. Furthermore, NGAL cancelled out the proliferative effects of fibroblast growth factor (FGF)-2 and epidermal growth factor (EGF) on chondrocytes from a patient with RA and proliferative effect of FGF-2 on chondrosarcoma cells.

Conclusions

Our results indicate that GM-CSF contributes to the pathogenesis of RA through upregulation of NGAL in neutrophils, followed by induction of TERA, cathepsin D and TG2 in synoviocytes. NGAL and the upregulated enzymes may therefore play an important role in RA.
Tamoxifen induces pleiotrophic changes in mammary stroma resulting in extracellular matrix that suppresses transformed phenotypes
Authors: Hattar Rhonda , Maller Ori , McDaniel Shauntae , Hansen Kirk C , Hedman Karla J , Lyons Traci R , Lucia Scott , Wilson R Storey , Schedin Pepper
Published: January 2009

Introduction

The functional unit of the mammary gland has been defined as the epithelial cell plus its microenvironment, a hypothesis that predicts changes in epithelial cell function will be accompanied by concurrent changes in mammary stroma. To test this hypothesis, the question was addressed of whether mammary stroma is functionally altered by the anti-oestrogen drug tamoxifen.

Methods

Forty female rats at 70 days of age were randomised to two groups of 20 and treated with 1.0 mg/kg tamoxifen or vehicle subcutaneously daily for 30 days, followed by a three-day wash out period. Mammary tissue was harvested and effects of tamoxifen on mammary epithelium and stroma determined.

Results

As expected, tamoxifen suppressed mammary alveolar development and mammary epithelial cell proliferation. Primary mammary fibroblasts isolated from tamoxifen-treated rats displayed a three-fold decrease in motility and incorporated less fibronectin in their substratum in comparison to control fibroblasts; attributes indicative of fibroblast quiescence. Immunohistochemistry analysis of CD68, a macrophage lysosomal marker, demonstrated a reduction in macrophage infiltration in mammary glands of tamoxifen-treated rats. Proteomic analyses by mass spectrometry identified several extracellular matrix (ECM) proteins with expression levels with tamoxifen treatment that were validated by Western blot. Mammary tissue from tamoxifen-treated rats had decreased fibronectin and increased collagen 1 levels. Further, ECM proteolysis was reduced in tamoxifen-treated rats as detected by reductions in fibronectin, laminin 1, laminin 5 and collagen 1 cleavage fragments. Consistent with suppression in ECM proteolysis with tamoxifen treatment, matrix metalloproteinase-2 levels and activity were decreased. Biochemically extracted mammary ECM from tamoxifen-treated rats suppressed in vitro macrophage motility, which was rescued by the addition of proteolysed collagen or fibronectin. Mammary ECM from tamoxifen-treated rats also suppressed breast tumour cell motility, invasion and haptotaxis, reduced organoid size in 3-dimensional culture and blocked tumour promotion in an orthotopic xenograft model; effects which could be partially reversed by the addition of exogenous fibronectin.

Conclusions

These data support the hypothesis that mammary stroma responds to tamoxifen treatment in concert with the epithelium and remodels to a microenvironment inhibitory to tumour cell progression. Reduced fibronectin levels and reduced ECM turnover appear to be hallmarks of the quiescent mammary microenvironment. These data may provide insight into attributes of a mammary microenvironment that facilitate tumour dormancy.
Balance of Irgm protein activities determines IFN-γ-induced host defense
Authors: Henry Stanley C , Daniell Xiaoju G , Burroughs Ashley R , Indaram Maanasa , Howell David N , Coers Jörn , Starnbach Michael N , Hunn Julia P , Howard Jonathan C , Feng Carl G , Sher Alan , Taylor Gregory A
Published: January 2009

The immunity-related GTPases (IRG), also known as p47 GTPases, are a family of proteins that are tightly regulated by IFNs at the transcriptional level and serve as key mediators of IFN-regulated resistance to intracellular bacteria and protozoa. Among the IRG proteins, loss of Irgm1 has the most profound impact on IFN-γ-induced host resistance at the physiological level. Surprisingly, the losses of host resistance seen in the absence of Irgm1 are sometimes more striking than those seen in the absence of IFN-γ. In the current work, we address the underlying mechanism. We find that in several contexts, another protein in the IRG family, Irgm3, functions to counter the effects of Irgm1. By creating mice that lack Irgm1 and Irgm3, we show that several phenotypes important to host resistance that are caused by Irgm1 deficiency are reversed by coincident Irgm3 deficiency; these include resistance to Salmonella typhimurium in vivo, the ability to affect IFN-γ-induced Salmonella killing in isolated macrophages, and the ability to regulate macrophage adhesion and motility in vitro. Other phenotypes that are caused by Irgm1 deficiency, including susceptibility to Toxoplasma gondii and the regulation of GKS IRG protein expression and localization, are not reversed but exacerbated when Irgm3 is also absent. These data suggest that members of the Irgm subfamily within the larger IRG family possess activities that can be opposing or cooperative depending on the context, and it is the balance of these activities that is pivotal in mediating IFN-γ-regulated host resistance.
Lipids regulate P2X7-receptor-dependent actin assembly by phagosomes via ADP translocation and ATP synthesis in the phagosome lumen
Authors: Kuehnel Mark. P. , Rybin Vladimir , Anand Paras K. , Anes Elsa , Griffiths Gareth
Published: January 2009

Latex bead phagosomes isolated from J774 macrophages polymerize actin. We show here that five lipids – phosphatidylinositol-4-phosphate, phosphatidylinositol-(4,5)-bisphosphate, sphingosine-1-phosphate (S1P), ceramide-1-phosphate and phosphatidic acid – stimulate both actin assembly and transport of ADP across the phagosomal membrane into the lumen. Once there, this ADP is converted to ATP by adenylate kinase activity. High luminal ATP concentrations correlated well with phagosome actin assembly under different conditions. The ATP-binding P2X7 receptor (P2X7R) was detected in phagosomes. Although S1P stimulated actin assembly by phagosomes from P2X7R-containing bone marrow macrophages, S1P-stimulated actin assembly was inhibited in phagosomes from cells lacking P2X7R. We propose that luminal ATP accumulates in response to selected lipids and activates the P2X7R that signals across the phagosomal membrane to trigger actin assembly on the cytoplasmic membrane surface. In the accompanying paper by Kuehnel et al. (doi:10.1242/jcs.034207), more evidence is provided in support of this model from the analysis of actin assembly at the plasma membrane of intact macrophages.
Sphingosine-1-phosphate receptors stimulate macrophage plasma-membrane actin assembly via ADP release, ATP synthesis and P2X7R activation
Authors: Kuehnel Mark P. , Reiss Miriam , Anand Paras K. , Treede Irina , Holzer Daniela , Hoffmann Eik , Klapperstueck Manuela , Steinberg Thomas H. , Markwardt Fritz , Griffiths Gareth
Published: January 2009

Eukaryotic plasma membranes assemble actin filaments within seconds of activation of many receptors, especially during chemotaxis. Here, serum or sphingosine-1-phosphate stimulation of J774 and RAW macrophages released ADP within seconds into the extracellular medium, along with an adenylate kinase activity that converted ADP to ATP. ATP then activated the P2X7 receptor (P2X7R) that was necessary for a peak of plasma-membrane actin assembly within 5 to 10 seconds in P2X7R-expressing J774, RAW and primary macrophages. Neither actin assembly nor characteristic P2X7R channel activity was seen in response to ATP in P2X7R-knockout macrophages, as detected by patch-clamp analysis. Since P2X7R has been shown previously to form a macromolecular complex with actin we propose that it is involved in the membrane assembly of actin. Our data reveal a surprisingly rapid and complex relay of signaling and externalization events that precede and control actin assembly induced by sphingosine-1-phosphate. The overall model we present is strongly supported by the data presented in the accompanying paper that focuses on latex bead phagosomes.
Functional suppression of E-cadherin by protein kinase Cδ
Authors: Chen Chien-Lin , Chen Hong-Chen
Published: January 2009

Protein kinase C (PKC) δ, a member of the novel PKC subfamily, has been shown to have an important role in cell proliferation, differentiation, apoptosis and cell motility. In this study, we investigated the effect of green fluorescent protein (GFP)-PKCδ and GFP-PKCα on cell-cell junctions of Madin-Darby canine kidney (MDCK) cells and found that only GFP-PKCδ suppressed the homophilic interactions between the ectodomains of E-cadherins, accompanied by a weaker cell-cell adhesion. The kinase-deficient mutant of GFP-PKCδ retained its localization at cell-cell junctions but failed to suppress the function of E-cadherin. In addition, we demonstrated that the hinge region (residues 280-347) that links the regulatory domain and the catalytic domain of PKCδ is essential for both its kinase activity and the targeting of cell-cell junctions. A PKCδ mutant with the deletion of amino acids 280-323 within the hinge region, which is catalytically active but defective in the targeting of cell-cell junctions, failed to suppress the function of E-cadherin. Moreover, expression of GFP-PKCδ in MDCK cells expedited the detachment of cells from their neighbors and facilitated cell scatter induced by hepatocyte growth factor. By contrast, the GFP-PKCδ mutants including the kinase-deficient mutant and the truncated mutant lacking residues 280-323 suppressed hepatocyte-growth-factor-induced cell scattering. Finally, siRNA-mediated knockdown of endogenous PKCδ in MDCK cells was found to delay the onset of cell-cell detachment and cell scattering induced by hepatocyte growth factor. Taken together, our results demonstrate that the catalytic activity of PKCδ and its localization to cell-cell junctions are necessary for PKCδ to suppress the function of E-cadherin, which thereby facilitates scattering of epithelial cells in response to extracellular cues.
Mechanically induced osteogenic differentiation – the role of RhoA, ROCKII and cytoskeletal dynamics
Authors: Arnsdorf Emily J. , Tummala Padmaja , Kwon Ronald Y. , Jacobs Christopher R.
Published: January 2009

Many biochemical factors regulating progenitor cell differentiation have been examined in detail; however, the role of the local mechanical environment on stem cell fate has only recently been investigated. In this study, we examined whether oscillatory fluid flow, an exogenous mechanical signal within bone, regulates osteogenic, adipogenic or chondrogenic differentiation of C3H10T1/2 murine mesenchymal stem cells by measuring Runx2, PPARγ and SOX9 gene expression, respectively. Furthermore, we hypothesized that the small GTPase RhoA and isometric tension within the actin cytoskeleton are essential in flow-induced differentiation. We found that oscillatory fluid flow induces the upregulation of Runx2, Sox9 and PPARγ, indicating that it has the potential to regulate transcription factors involved in multiple unique lineage pathways. Furthermore, we demonstrate that the small GTPase RhoA and its effector protein ROCKII regulate fluid-flow-induced osteogenic differentiation. Additionally, activated RhoA and fluid flow have an additive effect on Runx2 expression. Finally, we show RhoA activation and actin tension are negative regulators of both adipogenic and chondrogenic differentiation. However, an intact, dynamic actin cytoskeleton under tension is necessary for flow-induced gene expression.
Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis
Authors: Grob Alice , Roussel Pascal , Wright Jane E. , McStay Brian , Hernandez-Verdun Danièle , Sirri Valentina
Published: January 2009

Sirtuins, also designated class III histone deacetylases, are implicated in the regulation of cell division, apoptosis, DNA damage repair, genomic silencing and longevity. The nucleolar Sirtuin7 (SIRT7) was reported to be involved in the regulation of ribosomal gene (rDNA) transcription, but there are no data concerning the regulation of SIRT7 during the cell cycle. Here we have analyzed the behavior of endogenous SIRT7 during mitosis, while rDNA transcription is repressed. SIRT7 remains associated with nucleolar organizer regions, as does the RNA polymerase I machinery. SIRT7 directly interacts with the rDNA transcription factor UBF. Moreover, SIRT7 is phosphorylated via the CDK1-cyclin B pathway during mitosis and dephosphorylated by a phosphatase sensitive to okadaic acid at the exit from mitosis before onset of rDNA transcription. Interestingly, dephosphorylation events induce a conformational modification of the carboxy-terminal region of SIRT7 before the release of mitotic repression of rDNA transcription. As SIRT7 activity is required to resume rDNA transcription in telophase, we propose that this conformational modification regulates onset of rDNA transcription.
Effect of Transition-metal Oxide Additives for Water–Gas-shift Reaction over Supported Copper Catalyst
Authors: Sagata Kunimasa , Kawanishi Yusuke , Asamoto Makiko , Yamaura Hiroyuki , Yahiro Hidenori
Published: January 2009

The catalytic activities of the low-temperature water–gas-shift (LT-WGS) reaction were investigated for Al2O3-supported Cu catalysts containing CrOx, MnOx, FeOx, CoOx, NiOx, or ZnO. The catalytic activity of Cu/Al2O3 catalyst at 423 K was improved by the small addition of transition-metal oxide. In particular, Cu/Al2O3 with CoOx showed the highest activity among the supported Cu catalysts used in this study.
Preparation of Ultrathin Palladium Membrane Using Electrophoresis of Metallic Nanoparticles
Authors: Tominaga Aki , Nakagoe Osamu , Tanabe Shuji
Published: January 2009

A new procedure to prepare ultrathin membrane composed of nanoparticles was investigated. The nanoparticles were prepared in aqueous solution containing PdII ions by sonochemical reduction. Electrophoresis was used to fix the nanoparticles on a porous substrate disc. The ultrathin membrane was successfully prepared with the combination procedure, and the obtained Pd membrane showed high perm-selectivity for H2 and 3.85 of the separation factor of H2/N2 at room temperature.
Assembling into Chiral Crystal of Spin Crossover Iron(II) Complex
Authors: Sato Tetsuya , Iijima Seiichiro , Kojima Masaaki , Matsumoto Naohide
Published: January 2009

A new spin crossover iron(II) complex, [Fe(H2L2-Me)2]Cl2·2-PrOH·0.5H2O (1), has been prepared, where H2L2-Me = (2-methylimidazol-4-yl)methylidene)histamine. The complex is a chiral molecule due to octahedral coordinations of two tridentate ligands, they are linked by the hydrogen bonds of NH···Cl−···HN through Cl− ion into a chiral one-dimensional (1D) rod, and further the chiral rods with the same chirality are stacked to form a chiral crystal (conglomerate). The solvated sample showed a two-step SCO, and the desolvated sample showed an abrupt one-step SCO at T1⁄2=180 K.
Determination of 20(S)-Ginsenoside Rh1 and its Aglycone 20(S)-Protopanaxatriol in Rat Plasma by Sensitive LC-APCI-MS Method and its Application to Pharmacokinetic Study
Authors: Lai Li , Liu Yitong , Hao Haiping , Wang Guangji , Chen Xijing , Ren Hongcan
Published: January 2009

A liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) method has been developed for the measurement of the concentrations of 20(S)-ginsenoside Rh1 and its aglycone 20(S)-protopanaxatriol in rat plasma with panaxatriol as the internal standard. The method involved single liquid–liquid extraction of both 20(S)-ginsenoside Rh1 and 20(S)-protopanaxatriol from plasma samples with n-butanol. The limit of quantification (LOQ) was 5 ng mL−1 for both compounds. The method was validated within the linear range 5–2000 ng mL−1 for both compounds. The correlation coefficient for the calibration regression line was 0.999 or better. Intra-day and inter-day accuracy were better than 15%. The method has successfully been used for pharmacokinetic studies in rats. After intravenous administrations, the mean retention times of 20(S)-ginsenoside Rh1 and 20(S)-protopanaxatriol were 17.1 ± 2.0 min and 3.46 ± 0.33 h, respectively.
Fragmentation of a Non-Ester Pyrethroid Insecticide by Atmospheric Pressure Chemical Ionization
Authors: Itoh Nobuyasu , Kinumi Tomoya , Inagaki Shinsuke , Yarita Takashi
Published: January 2009

We elucidated the mechanism of fragmentation of ethophenprox (Mw = 376), a non-ester pyrethroid insecticide, in the presence of a proton, by using tandem mass spectrometry in combination with an atmospheric pressure chemical ionization technique in positive-ion mode. When methanol or acetonitrile was used as a solvent, no protonated ethophenprox ion was observed in the mass spectra even at low cone voltage (10V), at which solvent cluster ions can exist. Instead of the protonated ion, an unexpected m/z 359 ion was strongly observed under all conditions examined. The product ion spectrum of the m/z 359 ion obtained under low collision energy (20 eV) showed that this ion can be formed through structural rearrangement involving water loss mainly via the six-centered pathway in this system, although two pathways (five-centered and six-centered) to form the m/z 359 ion are suggested in the literature.
Gas-Phase Intramolecular Elimination Reaction Studies of Steviol Glycosides in Positive Electrospray and Tandem Mass Spectrometry
Authors: Upreti Mani , Clos John F. , Somayajula Kasi V. , Milanowski Dennis J. , Mocek Ulla , DuBois Grant E. , Prakash Indra
Published: January 2009

This paper reports the first study of the gas-phase intramolecular elimination reaction of steviol glycosides in positive electrospray mass spectrometry. The observed glycosylated product ions are proposed to be formed via an intramolecular elimination of sugar units from the parent molecule ion. It was further proven by MS/MS studies and deuterium labeling experiments with one of the steviol glycosides, rebaudioside A. These mass spectrometric results confirmed that the new glycosylated product ions observed are most likely formed by the combination of glucose moieties (Glu) II–IV and Glu I via a gas-phase intramolecular elimination reaction.