bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Disparities Among Health Care Workers
Authors: Mawn Barbara , Siqueira Eduardo , Koren Ainat , Slatin Craig , Devereaux Melillo Karen , Pearce Carole , Hoff Lee Ann
Published: November 2009

In this article we describe the process of an interdisciplinary case study that examined the social contexts of occupational and general health disparities among health care workers in two sets of New England hospitals and nursing homes. A political economy of the work environment framework guided the study, which incorporated dimensions related to market dynamics, technology, and political and economic power. The purpose of this article is to relate the challenges encountered in occupational health care settings and how these could have impacted the study results. An innovative data collection matrix that guided small-group analysis provided a firm foundation from which to make design modifications to address these challenges. Implications for policy and research include the use of a political and economic framework from which to frame future studies, and the need to maintain rigor while allowing flexibility in design to adapt to challenges in the field.
Informing Evidence: Claimsmaking in Midwives’ and Clients’ Talk About Interventions
Authors: McKenzie Pamela J. , Oliphant Tami
Published: November 2009

Communication for informed choice is particularly challenging in clinical settings such as direct-entry midwifery, where the care model embraces diverse therapies and forms of knowledge.We identified three discursive moves (explanation, invocation, and evaluation) that Ontario midwives and clients used in making claims about proposed interventions. The analysis was informed by an understanding of communication as an interactionally situated and socially constructed interpretive practice. Both midwives and women called on the authority of biomedical discourse, but they also turned to sources such as women’s wisdom to support their cases. The flexible use of these moves afforded participants considerable latitude in accepting or rejecting forms of evidence as authoritative. However, strategies designed to empower clients in making choices could unintentionally serve to enhance the authority of the care provider. Talk about interventions brings into view both the knowledge systems and the broader relations within which regulated midwifery practice operates.
Volunteer Research Subjects’ Experience of Participation in Research on a Novel Diagnostic Technology for Breast Cancer
Authors: Morris Norma , Schneider Margaret
Published: November 2009

Although volunteer research subjects play a crucial role in the development of new health technologies, there have been relatively few in-depth studies of what participation in research means to them, and how they manage and make sense of the research encounter. Using constructivist perspectives we analyze data from 15 United States-based women taking part in tests of prototype instrumentation with potential for cancer diagnosis, comparing their responses with findings from a larger study (using the same interview methodology) on United Kingdom-based women participating in a similar program. For both groups the prime concerns emerging at interview related to the social rather than the physical challenges of participation. Both deployed similar discursive strategies to manage these tensions.We suggest that, at least within the limits of the kind of low-risk, nontherapeutic research studied, lessons can be drawn for research management, particularly the key role of the researcher—researched working relationship in assuring mutually satisfactory outcomes.
Eshelby’s Problem for a Bonded Piezo-elastic Bimaterial
Authors: Sudak L.J.
Published: November 2009

A general method is presented for the analytic solution of Eshelby’s problem concerned with a smooth inclusion of arbitrary shape embedded within the elastic half-plane of a bonded piezoelectric—elastic bimaterial. Since the well-known Stroh formulation, on which almost all existing works on Eshelby’s problem in piezoelectric media has been based, breaks down for isotropic elastic materials, the solutions available in the literature cannot be applied directly. Consequently, the method of solution for the current problem involves a combination of Stroh’s formulation for piezoelectric materials and the well-known Muskhelishvili method for isotropic elastic bodies. The general solution is derived in terms of an auxiliary function which can be constructed using conformal mappings that map the exterior of the inclusion onto the exterior of the unit circle. To illustrate the method, the case of a dilatational inclusion is examined and detailed results are shown for the mean stress within a thermal elliptic inclusion.
Use of Pavement Marking Degradation Models to Develop a Pavement Marking Management System
Authors: Sasidharan Lekshmi , Karwa Vishesh , Donnell Eric T.
Published: November 2009

The Pennsylvania Department of Transportation collected periodic pavement marking retroreflectivity data on 88 roadway segments over a 1-year period from May 2007 through May 2008. The purpose of this effort was to use the data collected to develop a series of pavement marking degradation models that could be used to implement a management system. In this study, panel data models were used to estimate the service life of both waterborne and epoxy pavement markings because of the repeated retroreflectivity measurements recorded over time. It was found that pavement marking retroreflectivity decreases as the age of both epoxy and waterborne-paint pavement markings increase. White pavement markings were shown to have higher estimated service lives than yellow pavement markings. Traffic exposure was found to be negatively correlated with pavement marking retroreflectivity in the waterborne-paint analysis, but traffic exposure was not statistically significant in the epoxy pavement marking retroreflectivity model. A life cycle cost analysis showed that waterborne paints are more cost-effective than epoxy pavement markings if applied on a statewide basis.
A Control Sign Facility Design to Meet the New FHWA Minimum Sign Retroreflectivity Standards
Authors: Harris Elizabeth A. , Rasdorf William , Hummer Joseph E.
Published: November 2009

Minimum sign retroreflectivity standards issued by the Federal Highway Administration (FHWA) on January 29, 2008, have focused the attention of administrators and sign managers on improving the nighttime performance of traffic signs. To predict when a sign will need replacement, an agency will need to know when the retroreflectivity of signs with similar characteristics deteriorate to the minimum level established by the FHWA. Currently in the literature, there is limited information about the long-term deterioration behavior of ASTM Type III and IX signs. One way of achieving a better understanding of long-term sign deterioration is to establish an experimental sign retroreflectivity measurement facility (ESRMF). An ESRMF is an arrangement of signs in a controlled area that have their retroreflectivity measured at regular intervals to determine how it deteriorates as a function of time. This article shows how such a facility should look and why. A template is presented that can be used by agencies nationwide for collecting critical sign data to inform policy decisions.
HOV or General Purpose Lanes?
Authors: Burris Mark , Lipnicky Kevin
Published: November 2009

High occupancy vehicle (HOV) lanes are used as a congestion management tool in many areas to encourage carpooling and transit by offering faster, more reliable trips than general purpose lanes (GPLs). However, they draw criticism from some groups as some motorists believe that they are underused. This article uses extensive data sets to compare user costs, specifically time and fuel costs, for two scenarios—(1) a single reversible HOV lane and (2) a GPL in each direction on the Katy Freeway in Houston, Texas—over a variety of mode and time shifts. These two scenarios were chosen because they would require approximately the same amount of room in the median of the Katy Freeway. With both high occupancy/toll operations and slugging on the Katy Freeway, the authors set out to see if this highly used HOV lane was the best use of this valuable real estate. Or would a pair of GPLs have provided lower total travel costs? In almost all examined scenarios, the two GPLs case had lower user costs than the HOV lane case.
Investigating Degenerated Peripheralization in Urban India: The Case of Water Supply Infrastructure and Urban Governance in Chennai
Authors: Gopakumar Govind
Published: November 2009

Globalization is compressing the sequential spatial experience of environmental burdens in developing country cities through a process of space—time telescoping. With the introduction of neoliberal reform policies, Indian cities have also begun experiencing the effects of telescoped environmental burdens. A compelling theoretical perspective in this tradition suggests that large Indian cities now display a “degenerated peripheralization” whereby the experience of environmental burdens is becoming increasingly uneven between the urban core and its peripheries as a result of policy neglect. However, reliance on this theory overlooks how place-specific historical, social, and technical processes in the urban context often support a dynamic of active appropriation of resources from the periphery and core. Drawing on the histories of urban politicalization and the institutionalization of water supply infrastructure, this article will contextualize the process of peripheralization in the Indian metropolitan city of Chennai as an appropriative and exploitative one rather than a degenerated one.
Eldercide: A Gendered Examination of Elderly Homicide in the United States, 2000-2005
Authors: Krienert Jessie L. , Walsh Jeffrey A.
Published: November 2009

Eldercide is an increasing category of homicide affecting members of one of society’s most vulnerable populations. Despite attention from health officials, policy makers, researchers, the public, and the criminal justice system, there remains a dearth of knowledge about the phenomenon. Examination of extant empirical works reveals overreliance on small localized subsamples drawn frequently from medical examiner reports, underutilization of large national samples, brief temporal spans of data, and diffuse victim and offender profiles. This work, examining a large sample of reported incidents collected as part of the National Incident-Based Reporting System (NIBRS) for the period 2000-2005, addresses several limitations.This research examines victim, offender, and incident characteristics using chi-square tests and logistic regression to establish baseline findings and victim/offender profiles from a more comprehensive sample of data than prior studies have employed. Furthermore, the work examines the role of gender as a key to the dichotomy that exists in the literature between stranger-oriented eldercide and family violence—oriented eldercide. Results suggest notable gender differences with White males being the most frequent victims of eldercide, killed predominantly by offenders below the age of 45 compared to female victims who are most frequently killed by offenders above 45 years of age. Males are also more likely to be killed by a stranger compared to females who are most likely to be killed by a spouse or child. This work both corroborates and contrasts prior findings providing new insights and avenues for future study.
Structure, Culture, and Lethality: An Integrated Model Approach to American Indian Suicide and Homicide
Authors: Lanier Christina
Published: November 2009

Investigations of lethal violence in the United States have primarily focused on Whites and/or African Americans, generally ignoring American Indians. Interestingly, statistics indicate that homicide and suicide rates among American Indians are often higher than other racial/ethnic groups within the United States. In an attempt to understand these lethal violence patterns, the current study utilizes the integrated model of suicide and homicide to investigate the structural and cultural factors that contribute to the production and/or direction of American Indian lethal violence. Using data from the Indian Health Service, Centers for Disease Control and Prevention, and the U.S. Census Bureau, a modified lethal violence count (LVC) is used to examine the production of lethal violence among American Indians within U.S. counties as well as the suicide—homicide ratio (SHR) to unravel the etiological underpinnings of lethal violence. Findings indicate partial support for the integrated model with economic conditions and family disruption influencing these patterns of lethal violence.
Research Note: Courthouse Shootings 1907-2007
Authors: Etter Gregg W. , Swymeler Warren G.
Published: November 2009

As long as there have been courthouses, there has been a danger of violence surrounding them. Courthouses are a place where people take conflicts to be solved. The terrorist attacks of September 11, 2001 by foreign terrorists and the earlier 1995 attack against the Alfred P. Murrah Building in Oklahoma City by domestic terrorists has increased the awareness of the need for more security in public buildings. In this descriptive study of 500 sheriff’s departments across the United States, 114 courthouse shootings are examined for motive, weapon availability, and casualties occurred.
Religiosity as Self-Enhancement: A Meta-Analysis of the Relation Between Socially Desirable Responding and Religiosity
Authors: Sedikides Constantine , Gebauer Jochen E.
Published: November 2009

In a meta-analysis, the authors test the theoretical formulation that religiosity is a means for self-enhancement. The authors operationalized self-enhancement as socially desirable responding (SDR) and focused on three facets of religiosity: intrinsic, extrinsic, and religion-as-quest. Importantly, they assessed two moderators of the relation between SDR and religiosity. Macro-level culture reflected countries that varied in degree of religiosity (from high to low: United States, Canada, United Kingdom). Micro-level culture reflected U.S. universities high (Christian) versus low (secular) on religiosity. The results were generally consistent with the theoretical formulation. Both macro-level and micro-level culture moderated the relation between SDR and religiosity: This relation was more positive in samples that placed higher value on religiosity (United States > Canada > United Kingdom; Christian universities > secular universities). The evidence suggests that religiosity is partly in the service of self-enhancement.
A Terror Management Analysis of the Psychological Functions of Religion
Authors: Vail Kenneth E. , Rothschild Zachary K. , Weise Dave R. , Solomon Sheldon , Pyszczynski Tom , Greenberg Jeff
Published: November 2009

From a terror management theory (TMT) perspective, religion serves to manage the potential terror engendered by the uniquely human awareness of death by affording a sense of psychological security and hope of immortality. Although secular beliefs can also serve a terror management function, religious beliefs are particularly well suited to mitigate death anxiety because they are all encompassing, rely on concepts that are not easily disconfirmed, and promise literal immortality. Research is reviewed demonstrating that mortality salience produces increased belief in afterlife, supernatural agency, human ascension from nature, and spiritual distinctions between mind and body. The social costs and benefits of religious beliefs are considered and compared to those of secular worldviews. The terror management functions of, and benefits and costs associated with, different types of religious orientation, such as intrinsic religiosity, quest, and religious fundamentalism, are then examined. Finally, the TMT analysis is compared to other accounts of religion.
Convenience: a services perspective
Authors: Farquhar Jillian Dawes , Rowley Jennifer
Published: November 2009

This theoretical paper argues that the concept and construct of convenience is at the forefront of customer and user evaluation of service experiences and should play, therefore, a much more pivotal role in marketing theory than it does at present. With increasing evidence that convenience is important to customers, it is timely to revisit the concept with a view to developing a research agenda that delivers an improved understanding of the nature of convenience. Accordingly, the paper concludes by proposing a definition of convenience and offering questions for further research based on a critique of existing models of convenience, and on the positioning of convenience in relation to associated concepts such as customer value, co-production and experiential consumption.
I just tend to wear what I like: contemporary consumption and the paradoxical construction of individuality
Authors: Newholm Terry , Hopkinson Gillian C.
Published: November 2009

Recent theoretical arguments about the inter-locking of identity and consumption pose a challenge to individuality. We explore this initially through literatures relating to the paradox that arises from the role of the (fashion) code and the use of social groupings in the production of the self through consumption practices. Then we explore individuality through narrative data collected by multiple methods in two studies. Detailed analysis of consumption accounts shows the marking of one’s individuality to be an important, if often precarious, accomplishment. Rhetorical devices we associate with this accomplishment include the rejection of the dictates of mass fashion and branding, the development of a personal choice rationale and the definition of the self as somehow different from a mass other. We argue that the consumer paradox exists but is more or less successfully resolved through such devices. In resolution of the paradox we suggest that while the consumer collective is semiotically represented, representations of individuality are adequately and locally narrated.
A New Look at Humility: Exploring the Humility Concept and Its Role in Socialized Charismatic Leadership
Authors: Nielsen Rob , Marrone Jennifer A. , Slay Holly S.
Published: November 2009

This theoretical piece advances humility’s role in socialized charismatic leadership by considering humility’s impact on the behaviors and effectiveness of this type of leadership. First, the authors propose humility as an important but overlooked antecedent to effective socialized charismatic leadership. As described primarily in extant personality and social psychology literatures, humility prevents excessive self-focus and allows for an understanding of oneself, in addition to perspective of one’s relationship with others. Second, the effects of humility on the display and effectiveness of three key socialized charismatic leader behaviors are considered. Theoretical contributions and future research directions are discussed.
The Feedback-Seeking Personality: Big Five and Feedback-Seeking Behavior
Authors: Krasman Joe
Published: November 2009

This study examined the influence of the Big Five domains of personality on six combinations of feedback-seeking behavior. A survey was completed by 130 full-time employees and showed the following results: Neuroticism increased indirect inquiry from supervisors and direct and indirect inquiry from coworkers. Extraversion increased direct and indirect inquiry from supervisors. Openness to experience increased reflective appraisal from supervisors and coworkers. Conscientiousness increased direct inquiry from supervisors. Agreeableness did not influence any of the feedback-seeking combinations. The variability in feedback-seeking behavior explained by the Big Five ranged from 4.2% to 7.6%. Results of this study indicate that a person’s feedback-seeking behavior is partially attributable to his or her personality makeup.
Sesamol down-regulates the lipopolysaccharide-induced inflammatory response by inhibiting nuclear factor-kappa B activation
Authors: Chu Pei-Yi , Hsu Dur-Zong , Hsu Pin-Yen , Liu Ming-Yie
Published: November 2009

We examined the effects of sesamol on the lipopolysaccharide (LPS)-induced inflammatory response. Sesamol inhibited serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β and nitrite production in LPS-treated mice, and inhibited LPS-induced inducible nitric oxide synthase expression in mouse leukocytes. Sesamol also down-regulated TNF-α, IL-1β, and nitrite production as well as inducible nitric oxide synthase expression in LPS-treated RAW 264.7 cells. Further, sesamol inhibited LPS-induced nuclear factor (NF)-κB translocation and inhibitor (I)κB-α phosphorylation in RAW 264.7 cells. By inhibiting TNF-α, IL-1β, and nitrite levels, and interfering with the NFκB pathway, sesamol down-regulated the LPS-initiated inflammatory response.
Rap1 controls lymphocyte adhesion cascade and interstitial migration within lymph nodes in RAPL-dependent and -independent manners
Authors: Ebisuno Yukihiko , Katagiri Koko , Katakai Tomoya , Ueda Yoshihiro , Nemoto Tomomi , Inada Hiroyuki , Nabekura Junichi , Okada Takaharu , Kannagi Reiji , Tanaka Toshiyuki , Miyasaka Masayuki , Hogg Nancy , Kinashi Tatsuo
Published: November 2009

The small GTPase Rap1 and its effector RAPL regulate lymphocyte adhesion and motility. However, their precise regulatory roles in the adhesion cascade preceding entry into lymph nodes and during interstitial migration are unclear. Here, we show that Rap1 is indispensably required for the chemokine-triggered initial arrest step of rolling lymphocytes through LFA-1, whereas RAPL is not involved in rapid arrest. RAPL and talin play a critical role in stabilizing lymphocyte arrest to the endothelium of blood vessels under flow or to the high endothelial venules of peripheral lymph nodes in vivo. Further, mutagenesis and peptide studies suggest that release of a trans-acting restraint from the β2 cytoplasmic region of LFA-1 is critical for Rap1-dependent initial arrest. Rap1 or RAPL deficiency severely impaired lymphocyte motility over lymph node stromal cells in vitro, and RAPL deficiency impaired high-velocity directional movement within lymph nodes. These findings reveal the several critical steps of Rap1, which are RAPL-dependent and -independent, in lymphocyte trafficking.
DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia
Authors: Milani Lili , Lundmark Anders , Kiialainen Anna , Nordlund Jessica , Flaegstad Trond , Forestier Erik , Heyman Mats , Jonmundsson Gudmundur , Kanerva Jukka , Schmiegelow Kjeld , Söderhäll Stefan , Gustafsson Mats G. , Lönnerholm Gudmar , Syvänen Ann-Christine
Published: November 2009

Despite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320 CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve stratification of ALL patients. The genes highlighted in our study are not enriched to specific pathways, but the gene expression levels are inversely correlated to the methylation levels.
Tumor necrosis factor–related apoptosis-inducing ligand 1 (TRAIL1) enhances the transition of red blood cells from the larval to adult type during metamorphosis in Xenopus
Authors: Tamura Kei , Mawaribuchi Shuuji , Yoshimoto Shin , Shiba Tadayoshi , Takamatsu Nobuhiko , Ito Michihiko
Published: November 2009

The transition of red blood cells (RBCs) from primitive to definitive erythropoiesis is conserved across vertebrates. In anuran amphibians, the larval RBCs from primitive erythropoiesis are replaced by adult RBCs from definitive erythropoiesis during metamorphosis. The molecular mechanisms by which the primitive (larval) blood cells are specifically removed from circulation are not yet understood. In this study, we identified Xenopus tumor necrosis factor–related apoptosis-inducing ligand 1 (xTRAIL1) and xTRAIL2 as ligands of Xenopus death receptor-Ms (xDR-Ms) and investigated whether TRAIL signaling could be involved in this transition. The Trail and xDR-M genes were highly expressed in the liver and RBCs, respectively, during metamorphosis. Interestingly, xTRAIL1 enhanced the transition of the RBCs, and a dominant-negative form of the xTRAIL1 receptor attenuated it, when injected into tadpoles. Moreover, xTRAIL1 induced apoptosis in larval RBCs, but had little effect on adult RBCs in vitro. We also found that adult RBCs treated with staurosporine, a protein kinase C (PKC) inhibitor, were sensitized to xTRAIL1. The mRNAs for PKC isoforms were up-regulated in RBCs during metamorphosis. These results suggest that xTRAIL1 can cause apoptosis, probably mediated through xDR-Ms, in larval RBCs, but may not kill adult RBCs, presumably owing to PKC activation, as part of the mechanism for RBC switching.
Immunomodulatory derivatives induce PU.1 down-regulation, myeloid maturation arrest, and neutropenia
Authors: Pal Rekha , Monaghan Sara A. , Hassett Andrea Cortese , Mapara Markus Y. , Schafer Peter , Roodman G. David , Ragni Margaret V. , Moscinski Lynn , List Alan , Lentzsch Suzanne
Published: November 2009

The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide yield high response rates in patients with multiple myeloma, but the use of IMiDs in multiple myeloma is associated with neutropenia and increased risk for venous thromboembolism (VTE) by mechanisms that are unknown. We show that IMiDs down-regulate PU.1, a key transcription factor involved in granulocyte differentiation in vitro and in patients treated with lenalidomide. Loss of PU.1 results in transient maturation arrest with medullary accumulation of immature myeloid precursors and subsequent neutropenia. Accumulation of promyelocytes leads to high levels of the platelet aggregation agonist, cathepsin G stored in the azurophilic granules of promyelocytes. High levels of cathepsin G subsequently may increase the risk of VTE. To our knowledge, this is the first report investigating the underlying mechanism of IMiD-induced neutropenia and increased risk of VTE in multiple myeloma.
The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas contains templated nucleotide insertions and a major breakpoint region similar to follicular and mantle cell lymphoma
Authors: Murga Penas Eva Maria , Callet-Bauchu Evelyne , Ye Hongtao , Gazzo Sophie , Berger Françoise , Schilling Georgia , Albert-Konetzny Nadine , Vettorazzi Eik , Salles Gilles , Wlodarska Iwona , Du Ming-Qing , Bokemeyer Carsten , Dierlamm Judith
Published: November 2009

The t(14;18)(q32;q21) involving the immunoglobulin heavy chain locus (IGH) and the MALT1 gene is a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. However, the nucleotide sequence of only one t(14;18)–positive MALT lymphoma has been reported so far. We here report the molecular characterization of the IGH-MALT1 fusion products in 5 new cases of t(14;18)–positive MALT lymphomas. Similar to the IGH-associated translocations in follicular and mantle cell lymphomas, the IGH-MALT1 junctions in MALT lymphoma showed all features of a recombination signal sequence–guided V(D)J-mediated translocation at the IGH locus. Furthermore, analogous to follicular and mantle cell lymphoma, templated nucleotides (T-nucleotides) were identified at the t(14;18)/IGH-MALT1 breakpoint junctions. On chromosome 18, we identified a novel major breakpoint region in MALT1 upstream of its coding region. Moreover, the presence of duplications of MALT1 nucleotides in one case suggests an underlying staggered DNA-break process not consistent with V(D)J-mediated recombination. The molecular characteristics of the t(14;18)/IGH-MALT1 resemble those found in the t(14;18)/IGH-BCL2 in follicular lymphoma and t(11;14)/CCND1-IGH in mantle cell lymphoma, suggesting that these translocations could be generated by common pathomechanisms involving illegitimate V(D)J-mediated recombination on IGH as well as new synthesis of T-nucleotides and nonhomologous end joining (NHEJ) or alternative NHEJ repair pathways on the IGH-translocation partner.
Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery
Authors: Crooks Daniel R. , Ghosh Manik C. , Haller Ronald G. , Tong Wing-Hang , Rouault Tracey A.
Published: November 2009

Mammalian ferrochelatase, the terminal enzyme in the heme biosynthetic pathway, possesses an iron-sulfur [2Fe-2S] cluster that does not participate in catalysis. We investigated ferrochelatase expression in iron-deficient erythropoietic tissues of mice lacking iron regulatory protein 2, in iron-deficient murine erythroleukemia cells, and in human patients with ISCU myopathy. Ferrochelatase activity and protein levels were dramatically decreased in Irp2−/− spleens, whereas ferrochelatase mRNA levels were increased, demonstrating posttranscriptional regulation of ferrochelatase in vivo. Translation of ferrochelatase mRNA was unchanged in iron-depleted murine erythroleukemia cells, and the stability of mature ferrochelatase protein was also unaffected. However, the stability of newly formed ferrochelatase protein was dramatically decreased during iron deficiency. Ferrochelatase was also severely depleted in muscle biopsies and cultured myoblasts from patients with ISCU myopathy, a disease caused by deficiency of a scaffold protein required for Fe-S cluster assembly. Together, these data suggest that decreased Fe-S cluster availability because of cellular iron depletion or impaired Fe-S cluster assembly causes reduced maturation and stabilization of apo-ferrochelatase, providing a direct link between Fe-S biogenesis and completion of heme biosynthesis. We propose that decreased heme biosynthesis resulting from impaired Fe-S cluster assembly can contribute to the pathogenesis of diseases caused by defective Fe-S cluster biogenesis.
Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants
Authors: Devreese Katrien , Peerlinck Kathelijne , Hoylaerts Marc F.
Published: November 2009

Lupus anticoagulants (LACs) are associated with thromboembolic complications (TECs). LACs can be detected by their anticoagulant properties in thrombin generation assays, by the peak height (PH) and lag time (LT). To assess the thrombotic risk in LAC-positive patients, we have expressed the LAC activity quantitatively by PH/LT calibration curves, constructed for mixtures of monoclonal antibodies against β2-glycoprotein I (β2GPI) and prothrombin, spiked in normal plasma. PH/LT was determined in LAC patients, with (n = 38) and without (n = 21) TECs and converted into arbitrary LAC units. LAC titers ranged from 0 to 200 AU/mL, with 5 of 59 patients being negative. In the positive LAC titer population (54 of 59), LAC and anti-β2GPI immunoglobulin G (IgG) titers correlated with TECs, with odds ratios of 3.54 (95% CI, 1.0-1.7) and 10.0 (95% CI, 1.98-50.6), respectively. In patients with single or combined low titers, useful predictions on thrombosis could be made only after additional measurements of soluble P-selectin and factor VII. This layered strategy yielded positive and negative predictive values, sensitivity, and specificity values approximately 90% in this subgroup. Hence, LAC and anti-β2GPI IgG titers, when combined with selected markers of the hypercoagulable state, allow a relevant thrombotic risk assessment in nearly all patients with LACs.
Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration
Authors: Subramanian Anuradha , Krishnan Uma Maheswari , Sethuraman Swaminathan
Published: November 2009

Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves.
PDGF-Rα gene expression predicts proliferation, but PDGF-A suppresses transdifferentiation of neonatal mouse lung myofibroblasts
Authors: Kimani Patricia W , Holmes Amey J , Grossmann Ruth E , McGowan Stephen E
Published: November 2009

Background

Platelet-derived growth factor A (PDGF-A) signals solely through PDGF-Rα, and is required for fibroblast proliferation and transdifferentiation (fibroblast to myofibroblast conversion) during alveolar development, because pdgfa-null mice lack both myofibroblasts and alveoli. However, these PDGF-A-mediated mechanisms remain incompletely defined. At postnatal days 4 and 12 (P4 and P12), using mouse lung fibroblasts, we examined (a) how PDGF-Rα correlates with ki67 (proliferation marker) or alpha-smooth muscle actin (αSMA, myofibroblast marker) expression, and (b) whether PDGF-A directly affects αSMA or modifies stimulation by transforming growth factor beta (TGFβ).

Methods

Using flow cytometry we examined PDGF-Rα, αSMA and Ki67 in mice which express green fluorescent protein (GFP) as a marker for PDGF-Rα expression. Using real-time RT-PCR we quantified αSMA mRNA in cultured Mlg neonatal mouse lung fibroblasts after treatment with PDGF-A, and/or TGFβ.

Results

The intensity of GFP-fluorescence enabled us to distinguish three groups of fibroblasts which exhibited absent, lower, or higher levels of PDGF-Rα. At P4, more of the higher than lower PDGF-Rα + fibroblasts contained Ki67 (Ki67+), and Ki67+ fibroblasts predominated in the αSMA + but not the αSMA- population. By P12, Ki67+ fibroblasts comprised a minority in both the PDGF-Rα + and αSMA+ populations. At P4, most Ki67+ fibroblasts were PDGF-Rα + and αSMA- whereas at P12, most Ki67+ fibroblasts were PDGF-Rα- and αSMA-. More of the PDGF-Rα + than - fibroblasts contained αSMA at both P4 and P12. In the lung, proximate αSMA was more abundant around nuclei in cells expressing high than low levels of PDGF-Rα at both P4 and P12. Nuclear SMAD 2/3 declined from P4 to P12 in PDGF-Rα-, but not in PDGF-Rα + cells. In Mlg fibroblasts, αSMA mRNA increased after exposure to TGFβ, but declined after treatment with PDGF-A.

Conclusion

During both septal eruption (P4) and elongation (P12), alveolar PDGF-Rα may enhance the propensity of fibroblasts to transdifferentiate rather than directly stimulate αSMA, which preferentially localizes to non-proliferating fibroblasts. In accordance, PDGF-Rα more dominantly influences fibroblast proliferation at P4 than at P12. In the lung, TGFβ may overshadow the antagonistic effects of PDGF-A/PDGF-Rα signaling, enhancing αSMA-abundance in PDGF-Rα-expressing fibroblasts.
The evolution of Brassica napus FLOWERING LOCUST paralogues in the context of inverted chromosomal duplication blocks
Authors: Wang Jing , Long Yan , Wu Baoduo , Liu Jia , Jiang Congcong , Shi Lei , Zhao Jianwei , King Graham J , Meng Jinling
Published: November 2009

Background

The gene FLOWERING LOCUS T (FT) and its orthologues play a central role in the integration of flowering signals within Arabidopsis and other diverse species. Multiple copies of FT, with different cis-intronic sequence, exist and appear to operate harmoniously within polyploid crop species such as Brassica napus (AACC), a member of the same plant family as Arabidopsis.

Results

We have identified six BnFT paralogues from the genome of B. napus and mapped them to six distinct regions, each of which is homologous to a common ancestral block (E) of Arabidopsis chromosome 1. Four of the six regions were present within inverted duplicated regions of chromosomes A7 and C6. The coding sequences of BnFT paralogues showed 92-99% identities to each other and 85-87% identity with that of Arabidopsis. However, two of the paralogues on chromosomes A2 and C2, BnA2.FT and BnC2.FT, were found to lack the distinctive CArG box that is located within intron 1 that has been shown in Arabidopsis to be the binding site for theFLC protein. Three BnFT paralogues (BnA2.FT, BnC6.FT.a and BnC6.FT.b) were associated with two major QTL clusters for flowering time. One of the QTLs encompassing two BnFT paralogues (BnC6.FT.a and BnC6.FT.b) on chromosome C6 was resolved further using near isogenic lines, specific alleles of which were both shown to promote flowering. Association analysis of the three BnFT paralogues across 55 cultivars of B. napus showed that the alleles detected in the original parents of the mapping population used to detect QTL (NY7 and Tapidor) were ubiquitous amongst spring and winter type cultivars of rapeseed. It was inferred that the ancestral FT homologues in Brassica evolved from two distinct copies, one of which was duplicated along with inversion of the associated chromosomal segment prior to the divergence of B. rapa (AA) and B. oleracea (CC). At least ten such inverted duplicated blocks (IDBs) were identified covering a quarter of the whole B. napus genome.

Conclusion

Six orthologues of Arabidopsis FT were identified and mapped in the genome of B. napus which sheds new light on the evolution of paralogues in polyploidy species. The allelic variation of BnFT paralogues results in functional differences affecting flowering time between winter and spring type cultivars of oilseed Brassica. The prevalent inverted duplicated blocks, two of which were located by four of the six BnFT paralogues, contributed to gene duplications and might represent predominant pathway of evolution in Brassica.
Phylogenomic analyses predict sistergroup relationship of nucleariids and Fungi and paraphyly of zygomycetes with significant support
Authors: Liu Yu , Steenkamp Emma T , Brinkmann Henner , Forget Lise , Philippe Hervé , Lang B Franz
Published: November 2009

Background

Resolving the evolutionary relationships among Fungi remains challenging because of their highly variable evolutionary rates, and lack of a close phylogenetic outgroup. Nucleariida, an enigmatic group of amoeboids, have been proposed to emerge close to the fungal-metazoan divergence and might fulfill this role. Yet, published phylogenies with up to five genes are without compelling statistical support, and genome-level data should be used to resolve this question with confidence.

Results

Our analyses with nuclear (118 proteins) and mitochondrial (13 proteins) data now robustly associate Nucleariida and Fungi as neighbors, an assemblage that we term 'Holomycota'. With Nucleariida as an outgroup, we revisit unresolved deep fungal relationships.

Conclusion

Our phylogenomic analysis provides significant support for the paraphyly of the traditional taxon Zygomycota, and contradicts a recent proposal to includeMortierellain a phylum Mucoromycotina. We further question the introduction of separate phyla for Glomeromycota and Blastocladiomycota, whose phylogenetic positions relative to other phyla remain unresolved even with genome-level datasets. Our results motivate broad sampling of additional genome sequences from these phyla.
Unique sequence features of the Human Adenovirus 31 complete genomic sequence are conserved in clinical isolates
Authors: Hofmayer Soeren , Madisch Ijad , Darr Sebastian , Rehren Fabienne , Heim Albert
Published: November 2009

Background

Human adenoviruses (HAdV) are causing a broad spectrum of diseases. One of the most severe forms of adenovirus infection is a disseminated disease resulting in significant morbidity and mortality. Several reports in recent years have identified HAdV-31 from species A (HAdV-A31) as a cause of disseminated disease in children following haematopoetic stem cell transplantation (hSCT) and liver transplantation. We sequenced and analyzed the complete genome of the HAdV-A31 prototype strain to uncover unique sequence motifs associated with its high virulence. Moreover, we sequenced coding regions known to be essential for tropism and virulence (early transcription units E1A, E3, E4, the fiber knob and the penton base) of HAdV-A31 clinical isolates from patients with disseminated disease.

Results

The genome size of HAdV-A31 is 33763 base pairs (bp) in length with a GC content of 46.36%. Nucleotide alignment to the closely related HAdV-A12 revealed an overall homology of 84.2%. The genome organization into early, intermediate and late regions is similar to HAdV-A12. Sequence analysis of the prototype strain showed unique sequence features such as an immunoglobulin-like domain in the species A specific gene product E3 CR1 beta and a potentially integrin binding RGD motif in the C-terminal region of the protein IX. These features were conserved in all analyzed clinical isolates. Overall, amino acid sequences of clinical isolates were highly conserved compared to the prototype (99.2 to 100%), but a synonymous/non synonymous ratio (S/N) of 2.36 in E3 CR1 beta suggested positive selection.

Conclusion

Unique sequence features of HAdV-A31 may enhance its ability to escape the host's immune surveillance and may facilitate a promiscuous tropism for various tissues. Moderate evolution of clinical isolates did not indicate the emergence of new HAdV-A31 subtypes in the recent years.
High throughput approaches reveal splicing of primary microRNA transcripts and tissue specific expression of mature microRNAs in Vitis vinifera
Authors: Mica Erica , Piccolo Viviana , Delledonne Massimo , Ferrarini Alberto , Pezzotti Mario , Casati Cesare , Del Fabbro Cristian , Valle Giorgio , Policriti Alberto , Morgante Michele , Pesole Graziano , Pè M Enrico , Horner David S
Published: November 2009

Background

MicroRNAs are short (~21 base) single stranded RNAs that, in plants, are generally coded by specific genes and cleaved specifically from hairpin precursors. MicroRNAs are critical for the regulation of multiple developmental, stress related and other physiological processes in plants. The recent annotation of the genome of the grapevine (Vitis vinifera L.) allowed the identification of many putative conserved microRNA precursors, grouped into multiple gene families.

Results

Here we use oligonucleotide arrays to provide the first indication that many of these microRNAs show differential expression patterns between tissues and during the maturation of fruit in the grapevine. Furthermore we demonstrate that whole transcriptome sequencing and deep-sequencing of small RNA fractions can be used both to identify which microRNA precursors are expressed in different tissues and to estimate genomic coordinates and patterns of splicing and alternative splicing for many primary miRNA transcripts.

Conclusion

Our results show that many microRNAs are differentially expressed in different tissues and during fruit maturation in the grapevine. Furthermore, the demonstration that whole transcriptome sequencing can be used to identify candidate splicing events and approximate primary microRNA transcript coordinates represents a significant step towards the large-scale elucidation of mechanisms regulating the expression of microRNAs at the transcriptional and post-transcriptional levels.
Arsenic transport by zebrafish aquaglyceroporins
Authors: Hamdi Mohamad , Sanchez Marco A , Beene Lauren C , Liu Qianyong , Landfear Scott M , Rosen Barry P , Liu Zijuan
Published: November 2009

Background

Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (AsIII) is one of the major species that exists environmentally. The transport of AsIII has been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct AsIII and its organic metabolite, monomethylarsenite (MAsIII). However, the transport of AsIII and MAsIII in in any fish species has not been characterized.

Results

In this study, five members of the aquaglyceroporin family from zebrafish (Danio rerio) were cloned, and their ability to transport water, glycerol, and trivalent arsenicals (AsIII and MAsIII) and antimonite (SbIII) was investigated. Genes for at least seven aquaglyceroporins have been annotated in the zebrafish genome project. Here, five genes which are close homologues to human AQP3, AQP9 and AQP10 were cloned from a zebrafish cDNA preparation. These genes were named aqp3, aqp3l, aqp9a, aqp9b and aqp10 according to their similarities to the corresponding human AQPs. Expression of aqp9a, aqp9b, aqp3, aqp3l and aqp10 in multiple zebrafish organs were examined by RT-PCR. Our results demonstrated that these aquaglyceroporins exhibited different tissue expression. They are all detected in more than one tissue. The ability of these five aquaglyceroporins to transport water, glycerol and the metalloids arsenic and antimony was examined following expression in oocytes from Xenopus leavis. Each of these channels showed substantial glycerol transport at equivalent rates. These aquaglyceroporins also facilitate uptake of inorganic AsIII, MAsIII and SbIII. Arsenic accumulation in fish larvae and in different tissues from adult zebrafish was studied following short-term arsenic exposure. The results showed that liver is the major organ of arsenic accumulation; other tissues such as gill, eye, heart, intestine muscle and skin also exhibited significant ability to accumulate arsenic. The zebrafish larvae also accumulate considerable amounts of arsenic.

Conclusion

This is the first molecular identification of fish arsenite transport systems and we propose that the extensive expression of the fish aquaglyceroporins and their ability to transport metalloids suggests that aquaglyceroporins are the major pathways for arsenic accumulation in a variety of zebrafish tissues. Uptake is one important step of arsenic metabolism. Our results will contribute to a new understanding of aquatic arsenic metabolism and will support the use of zebrafish as a new model system to study arsenic associated human diseases.