bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Adults’ Identity Exploration: Illustrations From Inside the “Camp Bubble”
Authors: Johnson Sara K. , Goldman Jane A. , Garey Anita I. , Britner Preston A. , Weaver Shannon E.
Published: September 2010

The study investigates the experiences of emerging adults who had worked as counselors at overnight summer camps; identity-related issues emerge as most salient in the analysis of in-depth interviews conducted with 12 women and 8 men from 8 camps. Their descriptions portray the identity exploration that took place within the camp context, through opportunities to try out roles and responsibilities ranging from the adult-like role model to the more child-like entertainer, and many counselors specifically remark on the role of camp experiences in their identity development. The role of camps as one type of facilitative venue for emerging adults’ identity exploration is discussed.
The Role of Romantic Partners, Family, and Peer Networks in Dating Couples’ Views About Cohabitation
Authors: Manning Wendy D. , Cohen Jessica A. , Smock Pamela J.
Published: September 2010

Emerging adults are increasingly cohabiting, but few studies have considered the role of social context in the formation of their views of cohabitation. Drawing on 40 semistructured interviews with dating couples, we explored the role of romantic partners, family, and peers on evaluations of cohabitation. In couples where each member had a differing view about cohabitation, one romantic partner’s desire to not cohabit trumped their partner’s more ambivalent feelings about cohabitation.The influence of family in the formation of cohabitation views was evident through a variety of mechanisms, including parental advice, social modeling, religious values, and economic control. Peers also played a key role, with couples using the vicarious trials of their peer networks to judge how cohabitation would affect their own relationship. By using a couple perspective, assessing reports from both members of each couple, this study showcases how beliefs about cohabitation are formed within an intimate dyad.
Online Polygamy or Virtual Bride
Authors: Batı Uğur , Atıcı Bünyamin
Published: September 2010

The developments that were experienced in the communication and technology area made Internet an important part of the daily life. In this respect, with the development of Internet, the changes in the social structure are closely connected with the lifestyles, attitudes, and behaviors of the people. In the study, the phenomena of virtual fellow wife and polygamy are researched and analyzed. A qualitative research, which is based on the observation fundamentally and richened with a survey and in-depth interviews, is carried out in accordance with the ethnographic research that is used in this study. The behavior-oriented observations are performed and the oral reports are arranged with the requirements that the research is performed in the natural environment. In the research, we see that two arguments such as “I have been never remorseful because I am brought/I come as a fellow wife virtually” and “Bringing a fellow wife is not a question, it is our tradition” showed the highest attitudes.
Arthropod colonisation of a debris-covered glacier
Authors: Gobbi Mauro , Isaia Marco , De Bernardi Fiorenza
Published: September 2010

The largest debris-covered glacier in the Alps (Miage Glacier, western Italian Alps) has been studied to explore the effects of debris-cover extent and depth on the spatial distribution of ground-dwelling arthropods. A multitaxa approach has been used to compare taxa richness and distribution to the functional role (dietary habits) of each taxon along the glacier tongue. Spiders and ground beetles have been studied in detail. Taxa richness declines with distance from the wooded sites (in front of the glacier tongue) to those above the glacier tongue. At each of the supraglacial sites, spiders, ground beetles, aphids, springtails and flies were found. A change in the dominance of the different functional roles was observed along the tongue. Wooded sites are characterised by predatory (e.g. spiders, beetles), detrivore (e.g. springtails and certain flies), phytophagous (e.g. aphids, certain beetles) and parasitoid (e.g. certain wasps) assemblages, whereas at the debris-covered sites, aphids, flies and springtails are likely to be prey for spiders and beetles. The species richness of the predominant predators (spiders and beetles) shows a positive relationship with vegetation cover and debris thickness. Two mutually exclusive spider and ground beetle assemblages were found; one within the debris cover and one within the wooded sites. In our opinion, debris-covered glaciers are acting as a refuge area for the cryophil stenotherm species living at higher altitudes which descend the glacial tongue to lower elevations. A similar hypothesis supports the biogeographical interpretation of the distribution of many boreo-alpine relict species in the Alps. We discuss our results in the light of possible future scenarios which suggest an increase in debris cover with global warming.
A conditional approach for inference in multivariate age-period-cohort models
Authors: Held Leonhard , Riebler Andrea
Published: September 2010

Age-period-cohort (APC) models are used to analyse data from disease registers given by age and time. When data are stratified by one further variable, for example geographical location, multivariate APC (MAPC) models can be applied to identify and estimate heterogeneous time trends across the different strata. In such models, outcomes share a set of parameters, typically the age effects, while the remaining parameters may differ across strata. In this article, we propose a conditional approach for inference to directly model relative time trends. We show that in certain situations the conditional approach can handle unmeasured confounding so that relative risks might be estimated with higher precision. Furthermore, we propose an extension for data with more stratification levels. Maximum likelihood estimation is performed using software for multinomial logistic regression. The usage of smoothing splines is suggested to stabilise estimates of relative time trends, if necessary. We apply the methodology to chronic obstructive pulmonary disease mortality data in England & Wales, stratified by three different areas and gender.
Review of Cancer Pain Management in Patients Receiving Maintenance Methadone Therapy
Authors: Rowley Dominic , McLean Sarah , O'Gorman Aisling , Ryan Karen , McQuillan Regina
Published: September 2010

Methadone is commonly used in the treatment of heroin addiction. Patients with a history of opioid misuse or on methadone maintenance therapy (MMT) with cancer often have difficult to manage pain. We studied 12 patients referred to the palliative care service with cancer pain who were on MMT. All had difficult to control pain, and a third required 5 or more analgesic agents. Two patients had documented ‘‘drug-seeking’’ behavior. Methadone was used subcutaneously as an analgesic agent in 1 patient. We explore why patients on MMT have difficult to manage pain, the optimal management of their pain, and the increasing role of methadone as an analgesic agent in cancer pain.
Development of a Japanese Benefit Finding Scale (JBFS) for Patients With Cancer
Authors: Ando Michiyo , Morita Tatsuya , Hirai Kei , Akechi Tatsuo , Kira Haruko , Ogasawara Eiko , Jingu Kenichi
Published: September 2010

The primary aim of this study was to develop a scale to evaluate benefits for patients with cancer under treatment in Japan (the Japan Benefit Finding scale [JBFS]). The participants were 98 patients with cancer who completed the JBFS, which has 26 items, the General Health Questionnaire short version (GHQ 12). Factor analysis, structural equation modeling (SEM), and correlation analysis were performed. Three key domains were identified: ‘‘Recognition of one’s role in the family and priorities,’’ ‘‘Appreciation for life,’’ and ‘‘Faith.’’ Validity was confirmed by SEM. There was a significant correlation between the JBFS and GHQ 12. The reliability and validity are adequate, and the JBFS shows that Japanese patients who found benefits in cancer were able to adjust to their disease.
Embedding Number-Combinations Practice Within Word-Problem Tutoring
Authors: Powell Sarah R. , Fuchs Lynn S. , Fuchs Douglas
Published: September 2010

Two aspects of mathematics with which students with mathematics learning difficulty (MLD) often struggle are word problems and number-combination skills. This article describes a math program in which students receive instruction on using algebraic equations to represent the underlying problem structure for three word-problem types. Students also learn counting strategies for answering number combinations that they cannot retrieve from memory. Results from randomized-control trials indicated that embedding the counting strategies for number combinations produces superior word-problem and number-combination outcomes for students with MLD beyond tutoring programs that focus exclusively on number combinations or word problems.
Strategies for Teaching Algebra to Students With Learning Disabilities: Making Research to Practice Connections
Authors: Strickland Tricia K. , Maccini Paula
Published: September 2010

To improve student success in mathematics, the use of research-based interventions is necessary to help secondary students with learning disabilities (LD) access the algebra curriculum. The authors provide an overview of the following research-based approaches: explicit instruction, graduated instructional sequence, technology, and graphic organizers. For each approach, a summary of the research is provided along with suggestions for how the approach can be used by classroom teachers to support algebra instruction.
Counting in Qualitative Research: Why to Conduct it, When to Avoid it, and When to Closet it
Authors: Hannah David R. , Lautsch Brenda A.
Published: September 2010

In this essay we discuss the issue of counting: the process of assigning numbers to data that are in nonnumerical form. We review why counting is a controversial issue in qualitative research, and explain how this controversy creates what we call the “multiple audience problem” for qualitative researchers. We then identify the purposes that can be served by four different types of counting, explore when counting should be avoided entirely, and discuss when the results of counting should be concealed, or as Sutton put it, kept in the closet.
Transaction Cost, Exchange Embeddedness, and Interlocal Cooperation in Local Public Goods Supply
Authors: Shrestha Manoj K. , Feiock Richard C.
Published: September 2010

The authors develop and test an integrated framework for understanding how transaction cost and exchange embeddedness contribute to the general problems of institutional collection action, contracting, and cooperation. An application of the framework to Georgia cities’ interlocal cooperative behavior across multiple services suggests that interlocal cooperation provides a viable alternative to both private contracting and hierarchical arrangements and that transaction characteristics—asset specificity and measurement difficulties—and reciprocal exchange relationship predict the participation and the amount of interlocal cooperation. A curvilinear relationship was discovered between transaction characteristics and interlocal cooperation that extends Williamson’s linear prediction.
Linking Party Platforms to Perceptions of Presidential Candidates’ Policy Positions, 1972–2000
Authors: Simas Elizabeth N. , Evans Kevin A.
Published: September 2010

If candidates sometimes seek to distinguish themselves from their parties and are ambiguous about their policy positions, to what extent do the policy platforms of parties affect individuals’ perceptions of presidential candidate positions? Using data from the American National Election Study and the Comparative Manifesto Project from 1972 to 2000, we show that citizens are able to use party platforms in their assessments of presidential candidates. We also demonstrate that an individual’s level of education is important in the process of linking Republican Party platforms to Republican presidential candidates. Our findings have important implications for the role of parties in presidential elections.
Political Awareness and Partisan Realignment
Authors: Claassen Ryan L.
Published: September 2010

Many attribute the demise of the solid South, and changes in party attachments outside the South, to elite-level changes in the parties’ positions on racial issues and an issue evolution of the party system. Support is also growing for the notion that, as the Republican Party became an acceptable alternative to the Democratic Party for racial issues in the South, a resurgence of class-based partisanship further fueled the exodus. By investigating whether political awareness mediates responsiveness to changes in the political environment, evidence that partisan evolution is concentrated among more aware citizens is uncovered, and the implications are examined.
State Supreme Courts and the Effects of Statutory Constraint
Authors: Randazzo Kirk A. , Waterman Richard W. , Fix Michael P.
Published: September 2010

Do state supreme court judges render decisions according to their ideological preferences, or are they constrained by the language of state statutes? Using data from the Judge-Level State Supreme Court Database, the authors analyze the votes of individual judges from 1995 to 1998 to determine whether their behavior is constrained by legislation. The results indicate that more detailed language (resulting in statutes with higher word counts) significantly limits the discretion afforded to liberal judges while simultaneously facilitating the ideological voting of their conservative colleagues.
Social Capital, Racial Diversity, and Equity
Authors: Hawes Daniel P. , Rocha Rene R.
Published: September 2010

Robert Putnam’s work suggests social capital is compatible with social equality, while Rodney Hero argues the two are inversely related. Hero and Putnam, however, are limited in their arguments because they have only cross-sectional data and their theoretical arguments imply dynamic relationships over time. We create a state-level social capital index and a measure of racial diversity that varies over time and across states. We use multivariate models to determine whether social capital or racial diversity better predicts levels of policy equity. We find that social capital detrimentally affects policy equity and racial diversity is positively associated with policy equity.
Tax Compliance as an Evolutionary Coordination Game: An Agent-Based Approach
Authors: Bloomquist Kim
Published: September 2010

Tax reporting compliance by small business owners is modeled in an agent-based framework using concepts and methods based on evolutionary dynamics. A business owner’s ‘‘fitness’’ is a function of net after tax (and post-audit) income. Business owners exhibit heterogeneous tax morale and compliance propensity following four stochastically assigned behavioral ‘‘archetypes’’: Honest, Strategic, Defiant, and Random. The model is calibrated to observations from laboratory experiments and taxpayer random audits. The calibrated model is used to simulate evolutionary changes in a static population of 10,000 small business owners. A simulation using realistic parameters for the probability of audit and penalty rate finds that after fifteen time periods, the initial number of Honest business owners declines by approximately one-third and are displaced by proprietors having either Defiant or Strategic compliance behaviors.
Evaluating the Science of Discovery in Complex Health Systems
Authors: Norman Cameron D. , Best Allan , Mortimer Sharon , Huerta Timothy , Buchan Alison
Published: September 2010

Complex health problems such as chronic disease or pandemics require knowledge that transcends disciplinary boundaries to generate solutions. Such transdisciplinary discovery requires researchers to work and collaborate across boundaries, combining elements of basic and applied science. At the same time, calls for more interdisciplinary health science acknowledge that there are few metrics to evaluate the products associated with these new ways of working. The Research on Academic Research (RoAR) initiative was established to evaluate the process of discovery and impact of collaboration that emerged through the Life Sciences Institute (LSI) at the University of British Columbia, a state-of-the-art facility designed to support researchers—self-organized around specific health problems rather than disciplines. A logic model depicting the factors influencing such collaboration is presented along with a multimethod evaluation plan to assist understanding of the discovery process in this new environment and develop new metrics for assessing collaborative impact.
Dishing up individual and collective dimensions in organizational knowing
Authors: Bouty Isabelle , Gomez Marie-Léandre
Published: September 2010

This article investigates the interplay between individual and collective dimensions in organizational knowing. We ground our analysis on the case of a gourmet restaurant managed by three different head chefs over an eight-year observation window from 2000 to 2008. We find organizational differences between the three periods although apart from head chef changes, the cooking team itself remained stable. Building on a parallel between knowing and habitus, we take into account the chefs’ trajectories, the ‘doing’ of agents in the organization, and organization and field characteristics. We show that in each period, the chef ’s knowing deeply permeated the restaurant. We demonstrate that the individual, collective, organizational and even field dimensions form a system of interdependence in knowing, where each dimension influences and is influenced by the others. Emphasizing the bidirectional nature of these relationships, we argue that a relational approach is necessary to better understand knowing.
Entering a new paradigm: emergency nursing into the 21st Century
Authors: Davies Kevin , Jones Bridie , Higginson Ray
Published: September 2010

Two National Audit Office reports were published in February 2010. The first was highly critical of emergency healthcare delivery in England and highlighted the ways in which staffing and resource allocations could be areas that could have a negative impact on morbidity and mortality. The second report highlighted the significant positive impact that current military emergency care is making with focused training and development of all professionals contributing to the care delivery strategies. This article evaluates the two publications and emphasises on the contribution that appropriately educated, prepared and trained emergency nurses could make within the NHS context.
A specific binding site for the prorenin propart peptide Arg10-Arg20 does not occur on human endothelial cells
Authors: Leckie Brenda J , Bottrill Andrew R
Published: September 2010

Introduction. We looked for novel binding sites for the human prorenin ‘decoy peptide’ sometimes called ‘handle region peptide’ on human endothelial cells.

Method. The biotinylated peptide biotin-Acp-RIFLKRMPSIR (B-PR), an unlabelled peptide PR1 (RIFLKRMPSIR) and a scrambled peptide scPR1 (SRRMIFPIKLR) were synthesized. B-PR was added to human umbilical cord endothelial cells (HUVECs) maintained in serum-free medium, with or without excess unlabelled peptide or ‘scrambled’ peptide as blocker. Biotin-labelled HUVEC proteins were extracted, the amount of bound tracer was measured, and the identity of the binding proteins was analysed by sodium-dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).

Results. Biotinylated peptide bound to the HUVEC proteins with a major labelled band at 68,600 ± 1503 kDa (mean ± SEM, n=5 runs). Unlabelled peptide and scrambled peptide equally displaced the labelled peptide, indicating that the binding was non-specific for amino acid sequence. LC-MS/MS showed that binding was mainly to cytoskeletal proteins.

Conclusion. The binding of the human prorenin peptide R10IFLKRMPSIR20 to HUVEC proteins is not specific for amino acid sequence and probably involves a general peptide/protein uptake mechanism. We could not detect a specific prorenin propart binding site in these cells.
End-of-life education in the pre-registration nursing curriculum: Patient, carer, nurse and student perspectives
Authors: Cavaye Joyce , Watts Jacqueline H.
Published: September 2010

Providing good quality care for dying patients has been highlighted as a national priority in the UK. The Department of Health’s end-of-life (EOL) care strategy outlines how patients should be cared for to ensure that they experience a ‘good death’. Nurses have an important role to play in the delivery of EOL care and need to be knowledgeable about the palliation of symptoms and the social context of death and dying. Traditionally, the pre-registration nursing curriculum has had a limited emphasis on EOL care. While there have been significant developments in nurse education in the last decade, the amount of EOL content in nurse education remains inadequate. Drawing on literature mainly from the UK and USA, this review explores from the perspectives of students, newly qualified nurses, patients and carers the outcomes of EOL education. It reviews the evidence to determine whether newly qualified nurses are adequately prepared to deliver quality care to patients at the end of their lives. The evidence suggests that despite a greater emphasis on EOL care in nurse training, adequately preparing nurses remains a challenge to educators.
Ready, willing and able? Specialist community public health nurses’ views of their public health role
Authors: Coverdale Gill
Published: September 2010

This paper is a report of a research study to explore specialist community public health nurses’ views of their public health role. Three key objectives were set: to identify what their public health role was; to explore what the influences are on that role are; to investigate what they felt the solutions were to enhance this aspect of their role.

The study design consisted of a small qualitative study that used three focus groups to collect data from practice teachers from health visiting, occupational health nursing and school nursing. The data was combined for thematic analysis of their responses to the three key topics identified. The results showed that the participants were somewhat knowledgeable about their role as public health nurses; were influenced by lack of resources, poor understanding from others of their role and tensions with managers and the wider team as to the importance of their public health role; and they offered solutions that included role clarity for effective skill mix, a shared vision for practice and debated the role of a specific public health nurse in the team. Recommendations for clear roles and responsibilities, clear protocols for assessing need and identifying priorities and performance management frameworks are offered.
New Media, Enduring Values
Authors: Brown Carrie , Groves Jonathan
Published: September 2010

This case study uses theory about organizational culture and leadership and multiple sources of evidence to evaluate the effectiveness of an initiative by three news organizations to bring the core principles of journalism to life on the web. A newspaper, a local television station, a producer and distributor of public radio, and an academic institution participated in this effort. Drawing upon participant observation and in-depth interviews, this study examines the role this emphasis on core values, so important to the professional identity of journalists, played in securing buy-in for the project and overcoming resistance to change, as well as other internal factors that negatively affected implementation, such as lack of sustained commitment and poor communication.
Social Media Under Social Control
Authors: Sivek Susan Currie
Published: September 2010

The process of socialization for new and future journalists will look dramatically different from the process undergone by previous generations of journalists because of economic realities and changes in the nature of news production. The rise of social media and their role in the establishment of a successful career will also affect the integration of these rising professionals into their employing organizations. These changes in the socialization process will require alterations both in the day-to-day management of these individuals and in the theoretical approaches to studying their work, particularly with regard to the impact of social media on the profession. This article demonstrates a wide range of concerns that media managers and researchers must consider as the journalism profession incorporates these new professionals into its ranks.
Clinical Results and Functional Evaluation of the Chrisman-Snook Procedure for Lateral Ankle Instability in Athletes
Authors: Kramer Dennis , Solomon Ruth , Curtis Christine , Zurakowski David , Micheli Lyle J.
Published: September 2010

There is no consensus regarding optimum surgical treatment for chronic ankle instability. The purpose of this study is to describe a variation of the Chrisman-Snook lateral ligament reconstruction that the senior author uses in patients with chronic ankle instability recalcitrant to conservative management. All patients who underwent reconstruction from 1997 to 2006 were identified, and those with a minimum 2-year follow-up were included, representing a total of 44 ankles in 43 patients. All underwent clinical evaluation and completion of the Foot and Ankle Outcome Survey and the Kaikkonen Scale. At mean follow-up of 4.4 years, mean dorsiflexion loss was 2° compared with the nonoperative side. The postoperative mean Foot and Ankle Outcome Survey score was 74 ± 16 (range, 36-98), while the mean Kaikkonen total score was 77 ± 14 (range, 40-95). Thirty-eight patients (84.6%) were satisfied with their result. Six patients (13.6%) underwent reoperation, including 4 with peroneal tendon scarring requiring tenolysis. Return to sport was achieved in 28 of 35 patients (80%) at a median of 6 months postoperatively. It is concluded that dorsiflexion loss can be minimized and return to sport expected in most patients following this variation of the Chrisman-Snook reconstruction.

Levels of Evidence: Therapeutic, Level IV
Effect of Bi deficiency on grain alignment of BiPb-2223 thin film fabricated using rf sputtering process and on critical current density properties
Authors: Aksan M. A. , Altin S. , Yakinci M. E. , Guldeste A. , Balci Y.
Published: September 2010

In the present study, thin films prepared as a function of the Bi concentration in the BiPbSrCaCuO system were synthesised. Thin films were fabricated using radio frequency sputtering method. Crystal structure of the films fabricated was determined from X-ray diffraction measurements. The crystal orientation was analysed by X-ray pole figure and in-plane alignment. Both X-ray diffraction and pole figure analysis revealed that crystallinity in the films decreased significantly with decreasing Bi concentration in the system. A systematic decrease in the superconducting transition temperature and hole concentration per CuO plane was obtained with decreasing Bi concentration. The Jc values of the films were calculated using Bean formula. It exhibits a significant dependence on the magnetic field and temperature. It was found that Jc decreased sharply with increasing applied magnetic field. The highest Jc value was found to be 1·06×106 A cm−2 at 10 K, which corresponded to the best flux pinning among the films fabricated.
Formation of ultrafine grained ferrite during thermomechanical treatment in microalloyed steel
Authors: Bhagat A N , Neelkant
Published: September 2010

In the present work, the formation of ultrafine grained ferrite has been studied by applying suitable thermomechanical treatment. A high amount of deformation (∼80%) at varying strain rates (0·01–10 s−1) was applied in the temperature range of Ar3 to Ac3 followed by water quenching. This treatment resulted in a two-phase ferrite–martensite microstructure as compared to fully martensite structure after quenching without deformation. The formation of ultrafine ferrite (⩽3 μm) during deformation was favourable at a lower temperature and a slower strain rate. A maximum ∼50% ferrite formed during deformation at 780°C with a strain rate of 0·01 s−1. Experimental rolling with a high strain (∼1·3) with finish rolling temperature just above Ar3 (∼750°C) resulted in fine ferrite–pearlite of ⩽3 μm, and the properties showed a high value of strength as compared to steels rolled in a conventional way. Dual phase microstructure (ferrite and martensite) was produced after partial austenisation to 780°C followed by quenching in water, and this resulted in an excellent combination of properties (high ultimate tensile strength, low yield strength/ultimate tensile strength, high elongation and high n values).
Fancd2
−/− mice have hematopoietic defects that can be partially corrected by resveratrol
Authors: Zhang Qing-Shuo , Marquez-Loza Laura , Eaton Laura , Duncan Andrew W. , Goldman Devorah C. , Anur Praveen , Watanabe-Smith Kevin , Rathbun R. Keaney , Fleming William H. , Bagby Grover C. , Grompe Markus
Published: September 2010

Progressive bone marrow failure is a major cause of morbidity and mortality in human Fanconi Anemia patients. In an effort to develop a Fanconi Anemia murine model to study bone marrow failure, we found that Fancd2−/− mice have readily measurable hematopoietic defects. Fancd2 deficiency was associated with a significant decline in the size of the c-Kit+Sca-1+Lineage− (KSL) pool and reduced stem cell repopulation and spleen colony-forming capacity. Fancd2−/− KSL cells showed an abnormal cell cycle status and loss of quiescence. In addition, the supportive function of the marrow microenvironment was compromised in Fancd2−/− mice. Treatment with Sirt1-mimetic and the antioxidant drug, resveratrol, maintained Fancd2−/− KSL cells in quiescence, improved the marrow microenvironment, partially corrected the abnormal cell cycle status, and significantly improved the spleen colony-forming capacity of Fancd2−/− bone marrow cells. We conclude that Fancd2−/− mice have readily quantifiable hematopoietic defects, and that this model is well suited for pharmacologic screening studies.
Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes
Authors: Barker Juliet N. , Doubrovina Ekaterina , Sauter Craig , Jaroscak Jennifer J. , Perales Miguel A. , Doubrovin Mikhail , Prockop Susan E. , Koehne Guenther , O'Reilly Richard J.
Published: September 2010

Cellular therapy of Epstein-Barr virus (EBV)+ posttransplantation lymphoproliferative diseases (PTLD) in cord blood transplant (CBT) recipients is limited by lack of donor access and the donor's naive neonatal immune system. We therefore used partially human leukocyte antigen–matched third-party in vitro expanded EBV-specific cytotoxic T lymphocytes (CTLs) to treat 2 CBT recipients with life-threatening, donor-derived monoclonal EBV+ diffuse large B-cell lymphomas with extranodal involvement developing in the context of graft-versus-host disease. Both patients had failed immunosuppression taper and Rituximab. After 5 and 9 infusions of 106 EBV-CTL/kg, respectively, each patient achieved a sustained complete remission without toxicity or graft-versus-host disease. Each is alive without recurrence at 20 and 15 months, respectively, post–EBV-PTLD diagnosis. This approach demonstrates the efficacy of using “off-the-shelf,” virus-specific third-party CTLs restricted by human leukocyte antigens expressed by the tumor to treat otherwise lethal EBV-PTLD. Such therapy may also be applicable to the treatment of other infections and residual or recurrent malignancy after CBT.
Detection, evaluation, and management of iron-restricted erythropoiesis
Authors: Goodnough Lawrence Tim , Nemeth Elizabeta , Ganz Tomas
Published: September 2010

Progress in our understanding of iron-restricted erythropoiesis has been made possible by important advances in defining the molecular mechanisms of iron homeostasis. The detection and diagnostic classification of iron-restricted erythropoiesis can be a challenging process for the clinician. Newer assays for markers of inflammation may allow more targeted management of the anemia in these conditions. The availability of new intravenous iron preparations provides new options for the treatment of iron-restricted erythropoiesis. This review summarizes recent advances regarding the detection, evaluation, and management of iron-restricted erythropoiesis.
A PKA-Csk-pp60Src signaling pathway regulates the switch between endothelial cell invasion and cell-cell adhesion during vascular sprouting
Authors: Jin Hui , Garmy-Susini Barbara , Avraamides Christie J. , Stoletov Konstantin , Klemke Richard L. , Varner Judith A.
Published: September 2010

Angiogenesis is controlled by signals that stimulate motility in endothelial cells at the tips of vascular sprouts while maintaining cell-cell adhesion in the stalks of angiogenic sprouts. We show here that Gs-linked G protein–coupled receptor activation of cAMP-dependent protein kinase (PKA) plays an important role in regulating the switch between endothelial cell adhesion and migration by activating C-terminal Src kinase, leading to inhibition of pp60Src. Activated PKA blocks pp60Src-dependent vascular endot helial-cadherin phosphorylation, thereby stimulating cell-cell adhesion while suppressing endothelial cell polarization, motility, angiogenesis, and vascular permeability. Similar to the actions of Notch and Dll4, PKA activation blocks sprouting in newly forming embryonic blood vessels, while PKA inhibition promotes excessive sprouting in these vessels. These findings demonstrate that G protein–coupled receptors and PKA regulate vascular sprouting during angiogenesis by controlling endothelial cell migration and cell-cell adhesion through their actions on pp60Src.
Mitochondrial genotype in vulvar carcinoma - cuckoo in the nest
Authors: Klemba Aleksandra , Kowalewska Magdalena , Kukwa Wojciech , Tonska Katarzyna , Szybinska Aleksandra , Mossakowska Malgorzata , Scinska Anna , Golik Paweł , Koper Kamil , Radziszewski Jakub , Kukwa Andrzej , Czarnecka Anna M , Bartnik Ewa
Published: September 2010

Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the other hand, there is emerging evidence on the use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA status in VSCC patients, haplogroup distribution analysis and D-loop sequencing were performed. The results were compared with available data for the general Polish population, cancer free-centenarians as well as patients with endometrial and head and neck cancer. The obtained data were also compared with the current status of mitochondrial databases. Significant differences in haplogroup distribution between VSCC cohort, general Polish population and cancer-free centenarians cohort were found. Moreover, a correlation between the VSCC patients haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA polymorphisms was found in VSCC. Our results suggest that the mitochondrial genetic background may influence the risk of VSCC occurrence as well as susceptibility to HPV infection.
Transcriptional profile of maize roots under acid soil growth
Authors: Mattiello Lucia , Kirst Matias , da Silva Felipe R , Jorge Renato A , Menossi Marcelo
Published: September 2010

Background

Aluminum (Al) toxicity is one of the most important yield-limiting factors of many crops worldwide. The primary symptom of Al toxicity syndrome is the inhibition of root growth leading to poor water and nutrient absorption. Al tolerance has been extensively studied using hydroponic experiments. However, unlike soil conditions, this method does not address all of the components that are necessary for proper root growth and development. In the present study, we grew two maize genotypes with contrasting tolerance to Al in soil containing toxic levels of Al and then compared their transcriptomic responses.

Results

When grown in acid soil containing toxic levels of Al, the Al-sensitive genotype (S1587-17) showed greater root growth inhibition, more Al accumulation and more callose deposition in root tips than did the tolerant genotype (Cat100-6). Transcriptome profiling showed a higher number of genes differentially expressed in S1587-17 grown in acid soil, probably due to secondary effects of Al toxicity. Genes involved in the biosynthesis of organic acids, which are frequently associated with an Al tolerance response, were not differentially regulated in both genotypes after acid soil exposure. However, genes related to the biosynthesis of auxin, ethylene and lignin were up-regulated in the Al-sensitive genotype, indicating that these pathways might be associated with root growth inhibition. By comparing the two maize lines, we were able to discover genes up-regulated only in the Al-tolerant line that also presented higher absolute levels than those observed in the Al-sensitive line. These genes encoded a lipase hydrolase, a retinol dehydrogenase, a glycine-rich protein, a member of the WRKY transcriptional family and two unknown proteins.

Conclusions

This work provides the first characterization of the physiological and transcriptional responses of maize roots when grown in acid soil containing toxic levels of Al. The transcriptome profiles highlighted several pathways that are related to Al toxicity and tolerance during growth in acid soil. We found several genes that were not found in previous studies using hydroponic experiments, increasing our understanding of plant responses to acid soil. The use of two germplasms with markedly different Al tolerances allowed the identification of genes that are a valuable tool for assessing the mechanisms of Al tolerance in maize in acid soil.
Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol
Authors: Mishra Paras K , Tyagi Neetu , Sen Utpal , Joshua Irving G , Tyagi Suresh C
Published: September 2010

Background

Hyperhomocysteinemia (HHcy) and hyperglycemia cause diabetic cardiomyopathy by inducing oxidative stress and attenuating peroxisome proliferator- activated receptor (PPAR) gamma. However, their synergistic contribution is not clear.

Methods

Diabetic Akita (Ins2+/-) and hyperhomocysteinemic cystathionine beta synthase mutant (CBS+/-) were used for M-mode echocardiography at the age of four and twenty four weeks. The cardiac rings from WT, Akita and hybrid (Ins2+/-/CBS+/-) of Akita and CBS+/- were treated with different doses of acetylcholine (an endothelial dependent vasodilator). High performance liquid chromatography (HPLC) was performed for determining plasma homocysteine (Hcy) level in the above groups. Akita was treated with ciglitazone (CZ) - a PPAR gamma agonist and tempol-an anti-oxidant, separately and their effects on cardiac remodeling were assessed.

Results

At twenty four week, Akita mice were hyperglycemic and HHcy. They have increased end diastolic diameter (EDD). In their heart PPAR gamma, tissue inhibitor of metalloproteinase-4 (TIMP-4) and anti-oxidant thioredoxin were attenuated whereas matrix metalloproteinase (MMP)-9, TIMP-3 and NADPH oxidase 4 (NOX4) were induced. Interestingly, they showed synergism between HHcy and hyperglycemia for endothelial-myocyte (E-M) uncoupling. Additionally, treatment with CZ alleviated MMP-9 activity and fibrosis, and improved EDD. On the other hand, treatment with tempol reversed cardiac remodeling in part by restoring the expressions of TIMP-3,-4, thioredoxin and MMP-9.

Conclusions

Endogenous homocysteine exacerbates diabetic cardiomyopathy by attenuating PPAR gamma and inducing E-M uncoupling leading to diastolic dysfunction. PPAR gamma agonist and tempol mitigates oxidative stress and ameliorates diastolic dysfunction in diabetes.
Cytoplasmic- and extracellular-proteome analysis of Diplodia seriata: a phytopathogenic fungus involved in grapevine decline
Authors: Cobos Rebeca , Barreiro Carlos , Mateos Rosa María , Coque Juan-José R
Published: September 2010

Background

The phytopathogenic fungus Diplodia seriata, whose genome remains unsequenced, produces severe infections in fruit trees (fruit blight) and grapevines. In this crop is recognized as one of the most prominent pathogens involved in grapevine trunk disease (or grapevine decline). This pathology can result in the death of adult plants and therefore it produces severe economical losses all around the world. To date no genes or proteins have been characterized in D. seriata that are involved in the pathogenicity process. In an effort to help identify potential gene products associated with pathogenicity and to gain a better understanding of the biology of D. seriata, we initiated a proteome-level study of the fungal mycelia and secretome.

Results

Intracellular and secreted proteins from D. seriata collected from liquid cultures were separated using two-dimensional gel electrophoresis. About 550 cytoplasmic proteins were reproducibly present in 3 independent extractions, being 53 identified by peptide mass fingerprinting and tandem mass spectrometry. The secretome analysis showed 75 secreted proteins reproducibly present in 3 biological replicates, being 16 identified. Several of the proteins had been previously identified as virulence factors in other fungal strains, although their contribution to pathogenicity in D. seriata remained to be analyzed. When D. seriata was grown in a medium supplemented with carboxymethylcellulose, 3 proteins were up-regulated and 30 down-regulated. Within the up-regulated proteins, two were identified as alcohol dehydrogenase and mitochondrial peroxyrredoxin-1, suggesting that they could play a significant role in the pathogenicity process. As for the 30 down-regulated proteins, 9 were identified being several of them involved in carbohydrate metabolism.

Conclusions

This study is the first report on proteomics on D. seriata. The proteomic data obtained will be important to understand the pathogenicity process. In fact, several of the identified proteins have been reported as pathogenicity factors in other phytopathogenic fungi. Moreover, this proteomic analysis supposes a useful basis for deepening into D. seriata knowledge and will contribute to the development of the molecular biology of this fungal strain as it has been demonstrated by cloning the gene Prx 1 encoding mitochondrial peroxiredoxin-1 of D. seriata (the first gene to be cloned in this microorganism; data not shown).
Pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in gastric cancer: a case report
Authors: Wang Jun , Saukel George W , Garberoglio Carlos A , Srikureja Wichit , Hsueh Chung-Tsen
Published: September 2010

We report a 49-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen. He underwent esophagogastroduodenoscopy in September 2009, which revealed a 2-cm gastric ulcer on the lesser curvature proximal to angularis. Biopsy of gastric ulcer showed moderately differentiated adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and fluorescence in situ hybridization. Further workups with endoscopic ultrasound, computed tomography and positron emission tomography staged his cancer as T3N1M0. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, docetaxel and capecitabine without severe toxicities except grade 2 diarrhea near the completion of cycle 3 requiring discontinuation of capecitabine. Afterwards, he received total gastrectomy with extended D2 lymph node dissections showing pathological complete response. He went on to receive 3 more cycles of chemotherapy postoperatively. The role of trastuzumab as a part of perioperative therapy in gastric cancer overexpressing HER2 is worth further investigation.
Borrelia burgdorferistimulation of chemokine secretion by cells of monocyte lineage in patients with Lyme arthritis
Authors: Shin Junghee J , Strle Klemen , Glickstein Lisa J , Luster Andrew D , Steere Allen C
Published: September 2010

Introduction

Joint fluid in patients with Lyme arthritis often contains high levels of CCL4 and CCL2, which are chemoattractants for monocytes and some T cells, and CXCL9 and CXCL10, which are chemoattractants for CD4+ and CD8+ T effector cells. These chemokines are produced primarily by cells of monocyte lineage in TH1-type immune responses. Our goal was to begin to learn how infection with Borrelia burgdorferi leads to the secretion of these chemokines, using patient cell samples. We hypothesized that B. burgdorferi stimulates chemokine secretion from monocytes/macrophages in multiple ways, thereby linking innate and adaptive immune responses.

Methods

Peripheral blood mononuclear cells (PBMC) from 24 Lyme arthritis patients were stimulated with B. burgdorferi, interferon (IFN)-γ, or both, and the levels of CCL4, CCL2, CXCL9 and CXCL10 were measured in culture supernatants. CD14+ monocytes/macrophages from PBMC and synovial fluid mononuclear cells (SFMC) were stimulated in the same way, using available samples. CXCR3, the receptor for CXCL9 and CXCL10, and CCR5, the receptor for CCL4, were assessed on T cells from PBMC and SFMC.

Results

In patients with Lyme arthritis, B. burgdorferi but not IFN-γ induced PBMC to secrete CCL4 and CCL2, and B. burgdorferi and IFN-γ each stimulated the production of CXCL9 and CXCL10. However, with the CD14+ cell fraction, B. burgdorferi alone stimulated the secretion of CCL4; B. burgdorferi and IFN-γ together induced CCL2 secretion, and IFN-γ alone stimulated the secretion of CXCL9 and CXCL10. The percentage of T cells expressing CXCR3 or CCR5 was significantly greater in SFMC than PBMC, confirming that TH1 effector cells were recruited to inflamed joints. However, when stimulated with B. burgdorferi or IFN-γ, SFMC and PBMC responded similarly.

Conclusions

B. burgdorferi stimulates PBMC or CD14+ monocytes/macrophages directly to secrete CCL4, but spirochetal stimulation of other intermediate cells, which are present in PBMC, is required to induce CD14+ cells to secrete CCL2, CXCL9 and CXCL10. We conclude that B. burgdorferi stimulates monocytes/macrophages directly and indirectly to guide innate and adaptive immune responses in patients with Lyme arthritis.