bluuebunny/crossref_metadata_2025 huggingface dataset:
Atorvastatin therapy reduces interferon-regulated chemokine CXCL9 plasma levels in patients with systemic lupus erythematosus
Authors: Ferreira GA , Teixeira AL , Sato EI
Published: April 2010

A recent study showed transcriptional levels of interferon-inducible chemokines in peripheral blood cells were associated with disease activity and organ damage in systemic lupus erythematosus, and may be useful in monitoring disease activity and prognosis. Our objective was to evaluate the capacity of atorvastatin to reduce plasma levels of interferon-regulated chemokines (CCL2, CCL3 and CXCL9) and to study the correlation between these chemokines and disease activity in patients with systemic lupus erythematosus. Eighty-eight female patients with systemic lupus erythematosus were divided into two groups: 64 receiving 20 mg/day of atorvastatin (intervention group) and 24 without atorvastatin (control group). All patients were followed for 8 weeks. At baseline and after 8 weeks laboratory tests were performed for all patients. Plasma levels of chemokines were measured by ELISA using commercial kits (DuoSet, R&D Systems, Minneapolis, USA). In a univariate analysis we found correlation between CCL2, CCL3 and CXCL9 plasma levels and SLEDAI score. In the intervention group we observed a significant decrease in CXCL9 plasma levels comparing baseline and levels at the end of the study (p = 0.04); however, no differences were observed regarding CCL2 or CCL3 plasma levels in this study. No significant difference was observed in the plasma levels of these chemokines in the control group. We conclude that treatment with atorvastatin was associated with a significant decrease in the plasma levels of CXCL9 in patients with systemic lupus erythematosus. As the plasma levels of CXCL9 correlated with the SLEDAI score, we ask whether reducing levels of this chemokine could help to control systemic lupus erythematosus activity. Lupus (2010) 19, 927—934.
Enhancing Deep Learning: Lessons From the Introduction of Learning Teams in Management Education in France
Authors: Borredon Liz , Deffayet Sylvie , Baker Ann C. , Kolb David
Published: April 2010

Drawing from the reflective teaching and learning practices recommended in influential publications on learning styles, experiential learning, deep learning, and dialogue, the authors tested the concept of “learning teams” in the framework of a leadership program implemented for the first time in a top French management school ( Grande Ecole). Qualitative feedback and personal observations on the implementation and outcomes of using this new learning paradigm reveal that although the steps from teaching to learning initially tested for MBA students in the United States are widely accepted, there were unexpected obstacles and opportunities in setting up the model in France. Some of these differences can be attributed to culture, particularly to immensely different educational philosophies that shape attitudes and norms within French classrooms and to the notion of learning itself, which is normalized by the social expectations of careers in management forged in French history. This article provides the theoretical basis of the particular learning model tested, describes the conditions within which it was implemented in one French Grande Ecole , and reports unexpected obstacles and favorable outcomes of the teaching/learning experiences from a cross-cultural perspective. The authors conclude with recommendations on implementing learning models across cultures.
Gender in the Management Education Classroom: A Collaborative Learning Journey
Authors: Bilimoria Diana , O'Neil Deborah A. , Hopkins Margaret M. , Murphy Verena
Published: April 2010

In this article, the authors describe a classroom incident and their subsequent learnings about effectively managing issues of gender diversity in an MBA course titled “Women in Organizations.” The authors employ Kolb’s learning cycle as a framework for describing the incident ( concrete experience), reflecting on and discussing what occurred ( reflective observation), examining pertinent literature for possible explanations ( abstract conceptualization ), and devising practical strategies to mitigate such incidents in the future ( active experimentation). The study describes the collaborative learning journey in which the authors engaged as a team of instructors and researchers to make sense of this incident and refine their pedagogical practices. The article concludes by offering practical suggestions for improved pedagogy in management education settings, specifically fostering greater gender reflexivity in the classroom, and using functional subgrouping to encourage understanding and integration of differences.
Which Behavioral and Personality Characteristics Are Associated With Difficulties in Selective Attention?
Authors: Avisar Alon
Published: April 2010

Objective: The present study investigated the behavioral and personality profile associated with difficulties in selective attention. Method: A group of participants with ADHD were assessed for ADHD behaviors. Adults with ADHD ( n = 22) and without ADHD ( n = 84) were tested on the conjunctive visual-search task for selective attention and behavioral measures, including ADHD behaviors, Big Five dimension of personality, obsessive compulsive disorder (OCD) symptoms, and sensation-seeking behavior. Results: Correlations and multiple regression analysis (group was dummy coded) showed that ADHD behaviors were not related to search performance. However, poorer search performance was related to greater neuroticism, agreeableness, introversion, lower sensation seeking, and, marginally, to OCD symptoms. Conclusion: The study findings suggested that difficulties in selective attention are probably not associated with ADHD behaviors, but rather with personality traits characterized by preserving and avoiding high-stimulation behaviors.
Common Method Issues: An Introduction to the Feature Topic in Organizational Research Methods
Authors: Spector Paul E. , Brannick Michael T.
Published: April 2010

It is widely accepted that the method of measurement can affect observations made in scientific studies. Method variance is variance attributable to the method of measurement rather than the trait of interest, and when trait scores share methods of measurement, common method variance may distort observed relationships among the scores. This Organizational Research Methods Common Method Issues feature topic contains five articles that as a group discuss the nature of method variance, the likely effects it can have on observed relationships, how much method variance likely exists, and what can be done to remedy potential problems. In addition, these articles explore researchers’ beliefs about method variance.
Regional powers and security: A framework for understanding order within regional security complexes
Authors: Frazier Derrick , Stewart-Ingersoll Robert
Published: April 2010

In this article we propose a framework for understanding order within Regional Security Complexes (RSCs), focused upon the importance of regional powers. We argue that there are three factors to consider in adequately explaining regional security with respect to the influence of regional powers: structure, regional power roles, and regional power orientations. The first factor emphasizes the necessary but not sufficient attributes of power and capability for understanding regional security dynamics. The last two factors stress the importance of regional power behavior as being critical to the security process. To this end we highlight three specific roles and sets of orientations that when examined in the context of structural factors, provide a clearer picture of security orders in RSCs.
Improving public school teachers in Pakistan: challenges and opportunities
Authors: Hussain Rana , Ali Sajid
Published: April 2010

This article tries to respond to a basic question: ‘can in-service teachers of public sectors in Pakistan be reformed?’ The authors’ response to this question is: ‘yes, public teachers can be reformed, if contextual possibilities are exploited efficiently’. Although a straightforward and simplistic response to the question, this was felt necessary to counter an unfavourable bias against public sector teachers in Pakistan without recognizing the challenges that they face, and without recognizing the potential of many of the public teachers who continuously strive to change these negative perceptions. This article recognizes the potential of public teachers and shares a relatively successful example of improving competencies among public teachers to support the response — the Cluster-Based Mentoring Programme (CBMP). Important features of the programmes are described along with discussion on its effectiveness and sustainability.
Children should be seen and heard: the power of student voice in sustaining new teachers
Authors: Demetriou Helen , Wilson Elaine
Published: April 2010

Recent research has highlighted the merits of consulting children in both primary and secondary schools about their teaching and learning. This article looks at the effectiveness of pupil voice in not only maximizing the potential of pupils and students but also the consequences for helping teachers in turn — and especially newly qualified teachers, who might encounter obstacles during their early months of teaching. Interviews were conducted with 11 secondary school science teachers in their first three years of teaching in order to ascertain the quality of teaching and the degree to which teachers felt that they were successful in communicating the subject matter to their students. The findings showed that consulting young people is one way of responding to the needs of teachers as well as to the pupils themselves and we discuss the potential of pupil voice in harnessing the thoughts and feelings of pupils and ultimately achieving effective teaching and learning.
Having ‘learning difficulties’: the inclusive education of disabled girls and boys in Vietnam
Authors: Rydstrom Helle
Published: April 2010

This article examines the ‘inclusive education’ strategy in Vietnam and the extent to which it facilitates learning in students with disabilities. After the introduction of the doi moi (renewal) policy in 1986, Vietnamese society went through a period of rapid transformation, including the educational sector. Debates on teaching means, curricula, learning, and the inclusion of children with disabilities in public school classes increasingly became a focus of concern. Supported by international aid organizations, the Vietnamese government initiated the implementation of an ‘inclusive education’ program which aims at mainstreaming the public school system in order to include all students regardless of disabilities. Even though the partners involved in the introduction of the ‘Inclusive Education’ program into Vietnam usually refer to it as a success, my data indicate that the program tends to amplify already identified problems in the public educational system mainly caused by overloaded and abstract curricula and a pervasive rote-learning tradition. The article shows how girls — disabled girls, in particular — are susceptible to pedagogical setbacks in the public school system.
Classroom conditions for effective learning: hearing the voice of Key Stage 3 pupils
Authors: Hopkins Elizabeth
Published: April 2010

This article argues that accessing and taking note of the voice of pupils is critical in working towards removing barriers to effective learning. Pupil voice was accessed using an innovative form of group interview incorporating an Ishikawa or fishbone tool and card sorting exercise. The data were collected from 132 pupils, from Years 7 to 9 (aged 11 to 14) in three UK secondary schools. The techniques proved to be successful ways to help pupils to articulate their views. There was an immediacy and authenticity in the process, which generated 13 ‘classroom conditions’ that pupils felt were significant in securing effective learning. The 13 conditions potentially provide a grounded framework to engage teachers and student teachers in analysis, reflection and discussion regarding effective teaching skills and strategies.
Delivering quality-evaluated healthcare information in the era of Web 2.0: design implications for Intute: Health and Life Sciences
Authors: Abbott Robert
Published: April 2010

The internet, though an invaluable and ubiquitous resource for health-related information, is perceived as being undermined by concerns about quality and reliability. Some recent developments, by permitting so-called user-generated content to be published on the internet, exacerbate these concerns. The impact of these developments, mostly characterized as Web 2.0, on the use of healthcare educational and information resources is explored in this article. There is a recognized need for an authoritative service that can address issues of quality. Intute: Health and Life Sciences is one such service, and its design in the context of meeting current Web 2.0 expectations and addressing concerns about quality is the focus of the article.
A patient centred framework for improving LTC quality of life through Web 2.0 technology
Authors: Pulman Andy
Published: April 2010

The NHS and Social Care Model — a blueprint supporting organisations in improving services for people with long-term conditions (LTCs) — noted options to support people with LTCs might include technological tools supporting personalised care and choice and providing resources for patients to self-care and self-manage. Definitions concerning the integration of health information and support with Web 2.0 technology are primarily concerned with approaches from the healthcare perspective. There is a need to design a patient centred framework, encapsulating the use of Web 2.0 technology for people with LTCs who want to support, mitigate or improve quality of life. Existing theoretical frameworks offer a means of informing the design and measurement of this framework. This article describes how Web 2.0 technology could impact on the quality of life of individuals with LTCs and suggests a starting point for developing a theoretically informed patient centred framework.
Constructed charts of vaccination strategies
Authors: Gray Lincoln , McCabe Jennifer A. , Bernstein David
Published: April 2010

Various vaccination rates are mathematically modeled as if they simply spread from area to next nearest area across a ‘constructed landscape’ of developing countries. A technique that had previously been used to model the spread of diseases effectively models the spread of disease prevention. Multidimensional scaling successfully summarizes complex patterns in vaccination rates in developing countries as a ‘constructed chart’ from ‘functional distances’. Countries that have similar vaccination rates are close together in this constructed chart, and countries that have different rates are far apart, regardless of the physical distance between the countries. A statistically significant ( p < 0.001) chart was made of seven different vaccination rates (diphtheria, polio, measles in adults, measles in infants, tuberculosis in adults, tuberculosis in infants, and total percentage of routine epidemic vaccines financed by government) in 49 developing countries (from Belarus, Belize and Benin to Vietnam, Yemen and Zimbabwe).
Automating and simplifying the SOFA score in critically ill patients with cancer
Authors: Nates Joseph L. , Cárdenas-Turanzas Marylou , Wakefield Chris , Kish Wallace Susannah , Shaw Andrew , Samuels Joshua A. , Ensor Joe , Price Kristen J.
Published: April 2010

The aim was to demonstrate the performance of a modified version of the Sequential Organ Failure Assessment (SOFA) score to predict mortality in medical and surgical patients with cancer. We performed an electronic retrospective review of databases. We included adult patients with cancer admitted into a 53-bed ICU over 28 months. We electronically calculated a modified SOFA (mSOFA) score at admission. A majority of the patients were admitted into the surgical ICU. Of 328 nonsurvivors, 85.1 per cent were medical patients and only 14.9 per cent surgical patients. The mean admission mSOFA scores for medical and surgical patients were 4.7 ± 3.2 and 1.7 ± 1.9, respectively. The overall area under the curve (AUC) of the mSOFA score was 0.84. The AUCs for medical and surgical patients were 0.72 and 0.78, respectively. Our results demonstrate that electronic assessment of mSOFA score has potential in resource allocation decisions as well as in critical care outreach programs.
Immigration regimes and schooling regimes: Which countries promote successful immigrant incorporation?
Authors: Hochschild Jennifer L. , Cropper Porsha
Published: April 2010

While Canada is often described as the most and France as one of the least successful countries in the realm of immigrant incorporation, the question remains unresolved of how to evaluate a country’s policies for dealing with immigration and incorporation relative to that of others. Our strategy is to examine the relationships among (1) countries’ policies and practices with regard to admitting immigrants, (2) their educational policies for incorporating first- and second-generation immigrants, and (3) the educational achievement of immigrants and their children. We compare eight western industrialized countries. We find that immigration regimes, educational regimes, and schooling outcomes are linked distinctively in each country. States that are liberal, or effective, on one dimension may be relatively conservative, or ineffective, on another, and countries vary in their willingness and ability to help disadvantaged people achieve upward mobility through immigration and schooling. We conclude that, by some normative standards, France has a better immigration regime than Canada does. Overall, this study points to new ways to study immigration and new normative standards for judging states’ policies of incorporation.
Charter schools, choice, and distributive justice: What evidence do we need?
Authors: Strike Kenneth
Published: April 2010

This article looks at charter schools from the perspective of distributive justice. It suggests three principles of distributive justice that should be satisfied by schools: the adequacy principle, the equity principle, and the communicative principle. It also sketches the justice argument for charter schools and uses the three principles to examine it. The focus of the article concerns the kinds of evidence required to decide if charter schools promote distributive justice. It argues that a focus on distributive justice helps to formulate a suitably broad view of what evidence is required that serves as a corrective to the excessive emphasis on test scores that characterizes much of the empirical work on school reform. The article also considers the claim that charter schools are more effective than other public schools because they create competition. It argues that an alternative explanation of their (alleged) success is that they are more communal.
Shaping Leadership for Today: Mary Parker Follett’s Aesthetic
Authors: Bathurst Ralph , Monin Nanette
Published: April 2010

In this article we explore a view of Mary Parker Follett’s leadership writings that adopting an aesthetic lens un folds. Our approach leads us to images of circularity as experienced in both our own sensory response to her arguments as paradoxical, and as an image of her intellectual abstractions. This aesthetic inquiry values a paradoxical both-and over a bipolar either-or approach, and demonstrates that Follett’s pragmatism stems from her notion of integration and her use of circularity as a recurring leitmotif. Follett argues that leadership integration is contingent on a continual review of the total situation in all its complexity and fluidity. This leads to paradoxical notions of the subordinate role of the leader in organisational processes and the pre-eminence of leadership as an activity that concerns all actors regardless of their place within a hierarchy.
The Dramatistic Genre in Leadership Studies: Implications for Research and Practice
Authors: Sinha Paresha N.
Published: April 2010

Since the late 1980s, leadership theorists and researchers have appreciated the significance of leaders as makers of meaning. While this understanding has stimulated a greater need to link leadership to organizational symbolism and organizational sense-making issues, the focus on these issues has resulted in not insignificant dissatisfaction with conventional approaches to the study of leadership. In response, this article proposes a complementary alternative focus for research and practice in the leadership area. It advances the use of the symbolic and relational aspects of leadership as highlighted in the three subgenres of dramatism namely: Kenneth Burke’s dramatism (life is drama ), Erving Goffman’s dramaturgy (life is like drama ) and Victor Turner’s social drama (life and drama are interdependent ). There-after the article explores the key distinctions between the three sub-genres so as to identify their analytical as well as explanatory focus. Implications for leadership research and practice using the three subgenres are presented. The article closes with a discussion on the opportunities an integrated dramatistic approach might offer the general field of leadership.
Spirituality at Work, and its Implications for Leadership and Followership: A Post-structuralist Perspective
Authors: Tourish Dennis , Tourish Naheed
Published: April 2010

Recent years have witnessed a significant growth of interest in spirituality at work (SAW), and in particular in spirituality management and leadership development. This article argues that the literature in the area is replete with paradoxes, many of which may be irresolvable. These revolve around how spirituality is defined, with advocates variously stressing its religious dimensions, usually from a Christian perspective, and others articulating a more secular approach focusing on non-denominational humanistic values. Much of the literature assumes that the values of business leaders reflect unitarist rather than sectional interests. In exploring these contradictions, this article adopts a post-structuralist perspective to argue that SAW seeks to abolish the distinction between people’s work-based lives on the one hand, and their personal lives and value systems on the other. Influence is conceived in uni-directional terms: it flows from ‘spiritual’ and powerful leaders to more or less compliant followers, deemed to be in need of enlightenment, rather than vice versa. It enhances the influence of leaders over followers, on the assumption that stable, consistent and coherent follower identities can be manufactured, capable of facilitating the achievement of leaders’ goals. We argue that SAW therefore promotes constricting cultural and behavioural norms, and thus seeks to reinforce the power of leaders at the expense of autonomy for their followers. Rather than encourage leaders to abolish the distinction between the private and public spaces inhabited by followers, in the name of liberation, we conclude that these should be preserved and extended.
Management of antiphospholipid syndrome
Authors: Del Papa Nicoletta , Vaso Nikoleta
Published: April 2010

The antiphospholipid syndrome (APS) is an autoimmune disorder presenting with tissue injury in various organs related to large- or small-vessel thrombosis associated with antiphospholipid and antiprotein/phospholipid complex antibodies. Although the pathophysiology, diagnosis, and clinical scenario may seem clear and straightforward, a more detailed examination reveals a more complex and uncertain picture related to the management of APS. This article reviews the current situation relating to APS therapy by evaluating the different clinical features of the syndrome ranging from thrombosis to pregnancy complications together with new strategies and pharmacological approaches.
Sonographic Evaluation of Hypertrophic Pyloric Stenosis
Authors: Walker Kelli Anne
Published: April 2010

Hypertrophic pyloric stenosis (HPS) is a thickening of the pylorus muscle, which connects the stomach to the duodenum. The exact etiology of this condition is not known, but some believe it is an acquired condition occurring after birth. Most cases occur in infants three to six weeks old. Diagnostic medical sonography is a highly important tool used in the diagnosis of HPS. It does not involve any radiation exposure, which makes it safer for infants. Many key characteristics of this condition help to make an accurate diagnosis. Some cases are treated with medications, but most patients have surgery to correct this condition, which has a very good prognosis. This case demonstrates the typical sonographic appearance of a 3½-week-old infant with HPS.
Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice
Authors: Pawlinski Rafal , Wang Jian-Guo , Owens A. Phillip , Williams Julie , Antoniak Silvio , Tencati Michael , Luther Thomas , Rowley Jesse W. , Low Elizabeth N. , Weyrich Andrew S. , Mackman Nigel
Published: April 2010

Tissue factor (TF) is the primary activator of the coagulation cascade. During endotoxemia, TF expression leads to disseminated intravascular coagulation. However, the relative contribution of TF expression by different cell types to the activation of coagulation has not been defined. In this study, we investigated the effect of either a selective inhibition of TF expression or cell type-specific deletion of the TF gene (F3) on activation of coagulation in a mouse model of endotoxemia. We found that inhibition of TF on either hematopoietic or nonhematopoietic cells reduced plasma thrombin-antithrombin (TAT) levels 8 hours after administration of bacterial lipopolysaccharide (LPS). In addition, plasma TAT levels were significantly reduced in endotoxemic mice lacking the TF gene in either myeloid cells (TFflox/flox,LysMCre mice) or in both endothelial cells (ECs) and hematopoietic cells (TFflox/flox,Tie-2Cre mice). However, deletion of the TF gene in ECs alone had no effect on LPS-induced plasma TAT levels. Similar results were observed in mice lacking TF in vascular smooth muscle cells. Finally, we found that mouse platelets do not express TF pre-mRNA or mRNA. Our data demonstrate that in a mouse model of endotoxemia activation of the coagulation cascade is initiated by TF expressed by myeloid cells and an unidentified nonhematopoietic cell type(s).
Childhood abdominal pain in primary care: design and patient selection of the HONEUR abdominal pain cohort
Authors: Spee Leo AA , van den Hurk Arjan PJM , van Leeuwen Yvonne , Benninga Marc A , Bierma-Zeinstra Sita MA , Passchier Jan , Berger Marjolein Y
Published: April 2010

Background

Abdominal pain in children is a common complaint presented to the GP. However, the prognosis and prognostic factors of childhood abdominal pain are almost exclusively studied in referred children. This cohort study aims at describing prognosis and prognostic factors of childhood abdominal pain in primary care. In this paper we describe methods used for data-collection and determine possible selective recruitment.

Methods/Design

We conducted an observational, prospective cohort study with a 1-year follow-up. From May 2004 to March 2006, 53 Dutch GPs recruited consecutive children aged 4-17 years with a new episode of abdominal pain not preceded by a consultation for this complaint in the previous 3 months. Participants filled in standardized questionnaires, and faeces and urine were sampled. To evaluate selective recruitment, the electronic medical records of participating GPs were retrospectively searched for eligible non-included children.

Discussion

This study allows us to describe prognosis and prognostic factors of childhood abdominal pain in primary care. A total of 305 children were included of whom 142 (46.6%) met predefined criteria for chronic/recurrent abdominal pain at presentation; from the total group of eligible children identified from the electronic medical record, 27% were included. The included children were significantly younger than non-included children (mean age 8.49 and 9.20 years). In proportion to identified eligible children, significantly less children diagnosed with "gastroenteritis" (6.8%) and significantly more children with "generalized abdominal pain" (39%) were included compared to the 27% that was expected. This cohort represents young school-aged children consulting GPs for a new episode of abdominal pain, not diagnosed as gastroenteritis. Almost half of them fulfil the criteria for chronic abdominal pain at presentation.
Spontaneous feline mammary intraepithelial lesions as a model for human estrogen receptor- and progesterone receptor-negative breast lesions
Authors: Burrai Giovanni P , Mohammed Sulma I , Miller Margaret A , Marras Vincenzo , Pirino Salvatore , Addis Maria F , Uzzau Sergio , Antuofermo Elisabetta
Published: April 2010

Background

Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women.

Methods

Formalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medicine (Sassari, Italy). Histologic sections, stained with hematoxylin and eosin (HE), were evaluated for the presence of IELs in tissue adjacent to excised mammary tumors. Lesions were compared to those of humans. Immunohistochemistry for estrogen receptor (ER-alpha), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu) and Ki-67 was performed in IELs and adjacent tumor tissues.

Results

Intraepithelial lesions were found in 57 of 203 (28%) feline mammary specimens and were categorized as UH (27%), ADH (29%), and DCIS (44%). Most IELs with atypia (ADH and DCIS) were associated with mammary cancer (91%), whereas UH was associated with benign lesions in 53% of cases. Feline IELs were remarkably similar to human IELs. No ER or PR immunoreactivity was detected in intermediate-grade or high-grade DCIS or their associated malignant tumors. HER-2 protein overexpression was found in 27% of IELs.

Conclusion

The remarkable similarity of feline mammary IELs to those of humans, with the tendency to lose hormone receptor expression in atypical IELs, supports the cat as a possible model to study ER- and PR-negative breast lesions.
Intracellular targets of RGDS peptide in melanoma cells
Authors: Aguzzi Maria Simona , Fortugno Paola , Giampietri Claudia , Ragone Gianluca , Capogrossi Maurizio C. , Facchiano Antonio
Published: April 2010

Background

RGD-motif acts as a specific integrins-ligand and regulates a variety of cell-functions via extracellular action affecting cell-adhesion properties. However, increasing evidence identifies additional RGDS-functions at intracellular level. Previous reports show RGDS-internalization in endothelial cells, cardiomyocytes and lymphocytes, indicating intracellular targets such as caspase-8 and caspase-9, and suggest RGDS specific activity at cytoplasmic level. Given the role RGDS-peptides play in controlling proliferation and apoptosis in several cell types, investigating intracellular targets of RGDS in melanoma cells may un-reveal novel molecular targets and key pathways, potentially useful for a more effective approach to melanoma treatment.

Results

In the present study we show for the first time that RGDS-peptide is internalized in melanoma cells in a time-dependent way and exerts strong anti-proliferative and pro-apoptotic effects independently from its extracellular anti-adhesive action. RGES control-peptide did not show biological effects, as expected; nevertheless it is internalized, although with slower kinetics. Survivin, a known cell-cycle and survival-regulator is highly expressed in melanoma cells. Co-immunoprecipitation assays in cell lysates and overlay assays with the purified proteins showed that RGDS interacts with survivin, as well as with procaspase-3, -8 and -9. RGDS-peptide binding to survivin was found to be specific, at high affinity (Kd 27.5 μM) and located at the survivin C-terminus. RGDS-survivin interaction appeared to play a key role, since RGDS lost its anti-mitogenic effect in survivin-deprived cells with a specific siRNA.

Conclusions

RGDS inhibits melanoma growth with an adhesion-independent mechanism; it is internalized in melanoma cells and specifically interacts with survivin. The present data may indicate a novel role of RGDS-containing peptides physiologically released from the extracellular matrix and may suggest a possible novel anti-proliferation strategy in melanoma.
PI3Kp110-, Src-, FAK-dependent and DOCK2-independent migration and invasion of CXCL13-stimulated prostate cancer cells
Authors: El Haibi Christelle P. , Sharma Praveen K. , Singh Rajesh , Johnson Paul R. , Suttles Jill , Singh Shailesh , Lillard James W.
Published: April 2010

Background

Most prostate cancer (PCa)-related deaths are due to metastasis, which is mediated in part by chemokine receptor and corresponding ligand interaction. We have previously shown that PCa tissue and cell lines express high levels of the chemokine receptor CXCR5, than compared to their normal counterparts, and interaction of CXCR5 with its specific ligand (CXCL13) promoted PCa cell invasion, migration, and differential matrix metalloproteinase (MMP) expression. This study dissects some of the molecular mechanisms following CXCL13-CXCR5 interaction that mediate PCa cell migration and invasion.

Results

Using Western blot analysis, kinase-specific cell-based ELISAs, and migration and invasion assays, we show that PCa cell lines differentially express phosphoinositide-3 kinase (PI3K) catalytic subunit isoforms and dedicator of cytokinesis 2 (DOCK2). Specifically, we show that PC3 and normal prostatic epithelial (RWPE-1), but not LNCaP cell lines expressed DOCK2, while RWPE, PC3, and LNCaP cell lines expressed PI3K-p110α and -p110β. Moreover, PC3 selectively expressed PI3K-p110γ, but LNCaP and RWPE cell lines expressed PI3Kp110δ. CXCL13 caused CXCR5-dependent activation of the PI3Kp85α in LNCaP cells, and p85α as well as -p101 in PC3 cells. CXCL13-CXCR5 interaction regulated LNCaP and PC3 cell migration and invasion through extracellular signal-regulated kinase 1/2 (ERK1/2) activation that was primarily dependent on the PI3Kp110 isoform(s), Src, and focal adhesion kinase (FAK), but not DOCK2.

Conclusions

While additional studies will be needed to determine the PI3K-independent (i.e., DOCK2-mediated) and -dependent events that dictate PCa cell responsiveness to CXCL13, these data provide evidence of the existence of cell type- and stimulus-specific signaling events that support migration and invasion of PCa cells.
Role of inflammation in túbulo-interstitial damage associated to obstructive nephropathy
Authors: Grande María T , Pérez-Barriocanal Fernando , López-Novoa José M
Published: April 2010

Obstructive nephropathy is characterized by an inflammatory state in the kidney, that is promoted by cytokines and growth factors produced by damaged tubular cells, infiltrated macrophages and accumulated myofibroblasts. This inflammatory state contributes to tubular atrophy and interstitial fibrosis characteristic of obstructive nephropathy. Accumulation of leukocytes, especially macrophages and T lymphocytes, in the renal interstitium is strongly associated to the progression of renal injury. Proinflammatory cytokines, NF-κB activation, adhesion molecules, chemokines, growth factors, NO and oxidative stress contribute in different ways to progressive renal damage induced by obstructive nephropathy, as they induce leukocytes recruitment, tubular cell apoptosis and interstitial fibrosis. Increased angiotensin II production, increased oxidative stress and high levels of proinflammatory cytokines contribute to NF-κB activation which in turn induce the expression of adhesion molecules and chemokines responsible for leukocyte recruitment and iNOS and cytokines overexpression, which aggravates the inflammatory response in the damaged kidney. In this manuscript we revise the different events and regulatory mechanisms involved in inflammation associated to obstructive nephropathy.
Identification of super-infected Aedes triseriatus mosquitoes collected as eggs from the field and partial characterization of the infecting La Crosse viruses
Authors: Reese Sara M , Mossel Eric C , Beaty Meaghan K , Beck Eric T , Geske Dave , Blair Carol D , Beaty Barry J , Black William C
Published: April 2010

Background

La Crosse virus (LACV) is a pathogenic arbovirus that is transovarially transmitted by Aedes triseriatus mosquitoes and overwinters in diapausing eggs. However, previous models predicted transovarial transmission (TOT) to be insufficient to maintain LACV in nature.

Results

To investigate this issue, we reared mosquitoes from field-collected eggs and assayed adults individually for LACV antigen, viral RNA by RT-PCR, and infectious virus. The mosquitoes had three distinct infection phenotypes: 1) super infected (SI+) mosquitoes contained infectious virus, large accumulations of viral antigen and RNA and comprised 17 of 17,825 (0.09%) of assayed mosquitoes, 2) infected mosquitoes (I+) contained no detectable infectious virus, lesser amounts of viral antigen and RNA, and comprised 3.7% of mosquitoes, and 3) non-infected mosquitoes (I-) contained no detectable viral antigen, RNA, or infectious virus and comprised 96.21% of mosquitoes. SI+ mosquitoes were recovered in consecutive years at one field site, suggesting that lineages of TOT stably-infected and geographically isolated Ae. triseriatus exist in nature. Analyses of LACV genomes showed that SI+ isolates are not monophyletic nor phylogenetically distinct and that synonymous substitution rates exceed replacement rates in all genes and isolates. Analysis of singleton versus shared mutations (Fu and Li's F*) revealed that the SI+ LACV M segment, with a large and significant excess of intermediate-frequency alleles, evolves through disruptive selection that maintains SI+ alleles at higher frequencies than the average mutation rate. A QTN in the LACV NSm gene was detected in SI+ mosquitoes, but not in I+ mosquitoes. Four amino acid changes were detected in the LACV NSm gene from SI+ but not I+ mosquitoes from one site, and may condition vector super infection. In contrast to NSm, the NSs sequences of LACV from SI+ and I+ mosquitoes were identical.

Conclusions

SI+ mosquitoes may represent stabilized infections of Ae. triseriatus mosquitoes, which could maintain LACV in nature. A gene-for-gene interaction involving the viral NSm gene and a vector innate immune response gene may condition stabilized infection.
An HIV epidemic is ready to emerge in the Philippines
Authors: Farr Anna C , Wilson David P
Published: April 2010

Background

The state of the HIV epidemic in the Philippines has been described as “low and slow”, which is in stark contrast to many other countries in the region. A review of the conditions for HIV spread in the Philippines is necessary.

Methods

We evaluated the current epidemiology, trends in behaviour and public health response in the Philippines to identify factors that could account for the current HIV epidemic, as well as to review conditions that may be of concern for facilitating an emerging epidemic.

Results

The past control of HIV in the Philippines cannot be attributed to any single factor, nor is it necessarily a result of the actions of the Filipino government or other stakeholders. Likely reasons for the epidemic's slow development include: the country's geography is complicated; injecting drug use is relatively uncommon; a culture of sexual conservatism exists; sex workers tend to have few clients; anal sex is relatively uncommon; and circumcision rates are relatively high.

In contrast, there are numerous factors suggesting that HIV is increasing and ready to emerge at high rates, including: the lowest documented rates of condom use in Asia; increasing casual sexual activity; returning overseas Filipino workers from high‐prevalence settings; widespread misconceptions about HIV/AIDS; and high needle‐sharing rates among injecting drug users.

There was a three‐fold increase in the rate of HIV diagnoses in the Philippines between 2003 and 2008, and this has continued over the past year. HIV diagnoses rates have noticeably increased among men, particularly among bisexual and homosexual men (114% and 214% respective increases over 2003‐2008). The average age of diagnosis has also significantly decreased, from approximately 36 to 29 years.

Conclusions

Young adults, men who have sex with men, commercial sex workers, injecting drug users, overseas Filipino workers, and the sexual partners of people in these groups are particularly vulnerable to HIV infection. There is no guarantee that a large HIV epidemic will be avoided in the near future. Indeed, an expanding HIV epidemic is likely to be only a matter of time as the components for such an epidemic are already present in the Philippines.
A comparison of passive seismic monitoring of fracture stimulation from water and C O2 injection
Authors: Verdon James P. , Kendall J.-Michael , Maxwell Shawn C.
Published: April 2010

Hydraulic fracturing is used to create pathways for fluid migration and to stimulate production. Usually, water is the injected fluid, although alternative fluids such as carbon dioxide [Formula: see text] have been used recently. The amount of fracturing that [Formula: see text] can induce is also of interest for the security of carbon capture and storage. Hydraulic fracturing is usually monitored using passive seismic arrays, detecting microseismic events generated by the fracturing. It is of interest to compare the amount of seismicity that [Formula: see text] injection can generate in comparison with water. With this in mind, we have analyzed a passive seismic data set monitoring the injection of water and supercritical [Formula: see text] under very similar conditions, allowing us to make a direct comparison be-tween the fluids. We examined event locations and event magnitudes, and we used shear-wave splitting to image the fractures that are generated. For both fluids,the event locations map the formation of fractures moving away from the injection well with normals parallel to the minimum principal stress. The events during water injection are limited to the injection depth, while during [Formula: see text] injection, activity migrates above the injection depth. Event magnitudes are similar in both cases, and larger event magnitudes appear to correlate with higher injection pressures. Shear-wave splitting suggests that water injection generates more fractures, though the data quality is not good enough to make a robust conclusion about this. The comparability between water and [Formula: see text] injection means that lessons can be learned from the abundant experience of conventional water injection.
Transport of Prostaglandin F2α Pulses from the Uterus to the Ovary at the Time of Luteolysis in Ruminants Is Regulated by Prostaglandin Transporter-Mediated Mechanisms
Authors: Lee JeHoon , McCracken John A. , Banu Sakhila K. , Rodriguez Royce , Nithy Thamizh K. , Arosh Joe A.
Published: April 2010

In ruminants, prostaglandin F2α (PGF2α) is the uterine luteolytic hormone. During luteolysis, PGF2α is synthesized and released from the endometrium in a pulsatile pattern. The unique structure of the vascular utero-ovarian plexus (UOP) allows transport of luteolytic PGF2α pulses directly from the uterus to the ovary, thus bypassing the systemic circulation. However, the underlying molecular mechanism is not known. The objective of the present study was to determine a role for PG transporter protein (PGT) in the compartmental transport of PGF2α from uterus to ovary through the UOP at the time of luteolysis using the sheep as a ruminant model. [3H]PGF2α, with or without a PGT inhibitor, was infused into UOP, and PGF2α transport and PGT protein expression were determined. Results indicate that PGT protein is expressed in tunica intima, tunica media, and tunica adventitia of the utero-ovarian vein and the ovarian artery of the UOP, and the expression levels are higher on d 10–15 compared with d 3–6 of the estrous cycle. Pharmacological inhibition of PGT prevented transport of exogenous [3H]PGF2α as well as oxytocin-induced endogenous luteolytic PGF2α pulse up to 80% from uterine venous blood into ovarian arterial blood through the UOP at the time of luteolysis in sheep. Taken together, these results indicate that at the time of luteolysis, transport of PGF2α from uterus to ovary through the UOP is regulated by PGT-mediated mechanisms. These findings also suggest that impaired PGT-mediated transport of PGF2α from the utero-ovarian vein into the ovarian artery could adversely influence luteolysis and thus affect fertility in ruminants.
Chromogranin A and the Autonomic System: Decomposition of Heart Rate Variability and Rescue by Its Catestatin Fragment
Authors: Dev Nagendu B. , Gayen Jiaur R. , O'Connor Daniel T. , Mahata Sushil K.
Published: April 2010

Chromogranin A (CHGA/Chga) has been implicated in the genesis of systemic hypertension and consequent cardiac abnormalities. Catestatin (CST) (human CHGA352-372) replacement reduces blood pressure elevation and increases baroreflex sensitivity in Chga knockout (KO) mice. Because of the dampened baroreflex sensitivity, we reasoned that KO mice would display altered heart rate variability (HRV). Thus, we evaluated beat-to-beat measurements in HRV in wild-type (WT) and KO mice, before and after CST replacement. HR dynamics were evaluated by bipolar Einthoven electrocardiogram, with deconvolution into time and frequency domains, as well as Lorenz nonlinear return analyses. At baseline, HR was higher [444 ± 24 beats per minute (bpm)] in KO compared with WT (330 ± 18 bpm) mice. The total power in the HRV spectra was substantially diminished in KO animals. CST increased total power but only in KO mice. Each time-domain parameter was substantially lower in KO compared with WT mice, and the CST in the KO group could reverse the differences. Lorenz analysis revealed reductions in S1 (short axis perpendicular to the line of identity in the ellipse) and S2 (long axis along the line of identity in the ellipse) in KO animals, indicating that regulation of HRV is diminished in the parasympathetic and sympathetic domains. CST replacement caused restoration of both S1 and S2, in the KO group. These data suggest that Chga has a profound effect on autonomic tone to the heart and that its CST fragment is responsible for such actions. The results suggest future strategies for intervention in cardiovascular disorders accompanied by adverse HRV profiles.