bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Role for Copper/Zinc–Superoxide Dismutase in Preventing Spontaneous Intracerebral Hemorrhage During Acute and Chronic Hypertension in Mice
Authors: Wakisaka Yoshinobu , Chu Yi , Miller Jordan D. , Rosenberg Gary A. , Heistad Donald D.
Published: February 2010

Backgrounds and Purpose—

Superoxide is associated with spontaneous intracerebral hemorrhage (ICH) during hypertension. The goal of this study was to test the hypothesis that changes in superoxide, in genetically altered mice with deletion and overexpression of copper/zinc–superoxide dismutase (SOD1), modulate susceptibility to ICH.

Methods—

Chronic hypertension was produced by infusion of angiotensin II and an inhibitor of nitric oxide synthase in drinking water in SOD1 transgenic (SOD1Tg) mice, SOD1-deficient (SOD1
−/−
) mice, and their respective wild-type littermates. Acute hypertension was produced by daily injections of angiotensin II in some mice with chronic hypertension to produce ICH. We evaluated susceptibility to ICH, oxidative stress (superoxide, NAD[P]H oxidase activity, SOD activity), gene expression, and activity of matrix metalloproteinases.

Results—

Incidence, size, and number of ICHs were reduced in SOD1Tg mice and were increased in SOD1
−/−
mice compared with their wild-type littermates. Levels of superoxide increased in the brain even before developing ICH in wild-type littermates, whereas levels of superoxide remained low in SOD1Tg mice. Changes in level of matrix metalloproteinase-9 paralleled oxidative stress in SOD1Tg mice and wild-type littermates. Moreover, levels of superoxide and matrix metalloproteinase-9 were greater in SOD1
−/−
mice than wild-type littermates after induction of ICH. Active matrix metalloproteinases colocalized on cerebral vessels that appeared to lead toward regions with ICH.

Conclusions—

These results suggest that superoxide contributes to the pathogenesis of spontaneous ICH, possibly through activation of matrix metalloproteinase-9, and that SOD1 protects against spontaneous ICH during hypertension.
Ischemic Stroke in Cancer Patients With and Without Conventional Mechanisms
Authors: Kim Seon Gyeong , Hong Ji Man , Kim Hahn Young , Lee Jun , Chung Pil-Wook , Park Kwang-Yeol , Kim Gyeong-Moon , Lee Kwang Ho , Chung Chin-Sang , Bang Oh Young
Published: February 2010

Background and Methods—

To assess the precise mechanisms of stroke in cancer patients, we analyzed the data for cancer patients with acute ischemic stroke registered from 6 centers in South Korea. Clinical features, risk factors, diffusion-weighted imaging lesion patterns, and laboratory findings including
d
-dimer levels were compared between patients with conventional stroke mechanisms (CSMs) and cryptogenic group.

Results—

A total of 161 patients were included in this study: 97 (60.2%) patients in the CSM group and 64 (39.8%) in the cryptogenic group. Patients in the CSM group were older and vascular risk factors were more prevalent than in the cryptogenic group. Diffusion-weighted imaging patterns of multiple lesions involving multiple arterial territories were observed more frequently in the cryptogenic group than in the CSM group. In addition, levels of the
d
-dimer were higher in the cryptogenic group than in the CSM group (11.5±14.6 versus 3.6±10.3 μg/dL). In multivariate analysis, the diffusion-weighted imaging lesion pattern of multiple vascular territories (odds ratio, 11.2; 95% CI, 3.74 to 33.3), and
d
-dimer levels of >1.11 μg/dL (odds ratio, 10.6; 95% CI, 3.29 to 33.8) were associated independently with the cryptogenic group.

Conclusions—

Stroke outside of CSM occurred in a large number in cancer patients. In stroke patients with cancer,
d
-dimer levels and diffusion-weighted imaging lesion patterns may be helpful in early identification of non-CSMs (especially coagulopathy associated with cancer) and possibly in guiding preventive strategies for stroke.
Comprehensive Automated Quality Assurance of Daily Surface Observations
Authors: Durre Imke , Menne Matthew J. , Gleason Byron E. , Houston Tamara G. , Vose Russell S.
Published: February 2010

This paper describes a comprehensive set of fully automated quality assurance (QA) procedures for observations of daily surface temperature, precipitation, snowfall, and snow depth. The QA procedures are being applied operationally to the Global Historical Climatology Network (GHCN)-Daily dataset. Since these data are used for analyzing and monitoring variations in extremes, the QA system is designed to detect as many errors as possible while maintaining a low probability of falsely identifying true meteorological events as erroneous. The system consists of 19 carefully evaluated tests that detect duplicate data, climatological outliers, and various inconsistencies (internal, temporal, and spatial). Manual review of random samples of the values flagged as errors is used to set the threshold for each procedure such that its false-positive rate, or fraction of valid values identified as errors, is minimized. In addition, the tests are arranged in a deliberate sequence in which the performance of the later checks is enhanced by the error detection capabilities of the earlier tests. Based on an assessment of each individual check and a final evaluation for each element, the system identifies 3.6 million (0.24%) of the more than 1.5 billion maximum/minimum temperature, precipitation, snowfall, and snow depth values in GHCN-Daily as errors, has a false-positive rate of 1%−2%, and is effective at detecting both the grossest errors as well as more subtle inconsistencies among elements.
Asymmetry of Atmospheric Circulation Anomalies over the Western North Pacific between El Niño and La Niña*
Authors: Wu Bo , Li Tim , Zhou Tianjun
Published: February 2010

The asymmetry of the western North Pacific (WNP) low-level atmospheric circulation anomalies between the El Niño and La Niña mature winter is examined. An anomalous WNP cyclone (WNPC) center during La Niña tends to shift westward relative to an anomalous WNP anticyclone (WNPAC) center during El Niño. Two factors may contribute to this asymmetric response. The first factor is the longitudinal shifting of El Niño and La Niña anomalous heating. The composite negative precipitation anomaly center during La Niña is located farther to the west of the composite positive precipitation anomaly center during El Niño. The westward shift of the heating may further push the WNPC westward relative to the position of the WNPAC. The second factor is the amplitude asymmetry of sea surface temperature anomalies (SSTAs) in the WNP, namely, the amplitude of local cold SSTA during El Niño is greater than that of warm SSTA during La Niña. The asymmetry of SSTA is originated from the asymmetric SSTA tendencies during the ENSO developing summer. Although both precipitation and surface wind anomalies are approximately symmetric, the surface latent heat flux anomalies are highly asymmetric over the key WNP region, where the climate mean zonal wind speed is small. Both the anomalous westerly during El Niño and the anomalous easterly during La Niña in the region lead to an enhanced surface evaporation, strengthening (weakening) the enhancement of the cold (warm) SSTA in situ during El Niño (La Niña). The asymmetry of the SSTA in the WNP is further amplified due to anomalous wind differences between El Niño and La Niña in their mature winter. Atmospheric general circulation model experiments demonstrate that both factors contribute to the asymmetry between the WNPAC and WNPC. The asymmetric circulation in the WNP contributes to the asymmetry of temporal evolutions between El Niño and La Niña.
Observations of the Evolution of the Nocturnal and Convective Boundary Layers and the Structure of Open-Celled Convection on 14 June 2002
Authors: Bennett Lindsay J. , Weckwerth Tammy M. , Blyth Alan M. , Geerts Bart , Miao Qun , Richardson Yvette P.
Published: February 2010

The Boundary Layer Evolution (BLE) missions of the International H2O Project (IHOP_2002) were designed to provide comprehensive observations of the distribution of water vapor in the quiescent boundary layer and its evolution during the early morning. The case study discussed in this paper presents detailed observations of the development of the boundary layer from before sunrise through to the period of growth of the mature convective boundary layer (CBL) during the 14 June 2002 BLE mission. The large number of remote sensing platforms, including the multiple instruments collocated at the Homestead Profiling Site, provided a detailed set of measurements of the growth and structure of the CBL.

The observations describe the classic evolution of a daytime CBL, beginning with a shallow nocturnal boundary layer (NBL) below the remnants of the previous day’s mixed layer, or residual layer. The vertical distribution of humidity in these layers during the early morning was affected by advection of dry air and by gravity waves. About an hour after sunrise a CBL developed, and gradually deepened with time as it mixed out the NBL and residual layer. The growth of the top of the CBL was particularly well observed because of the strong vertical gradients in temperature, humidity, and aerosol concentration. As the CBL deepened and the average CBL wind speed decreased, the mode of convective organization evolved from horizontal convective rolls to open-celled convection. A unique set of detailed measurements of the structure of the open cells was obtained from multiple instruments including the Doppler-on-Wheels radar, the Mobile Integrated Profiling System wind profiler, and the Scanning Raman lidar. They showed the relationship between open cells, thermals, mantle echoes, and the CBL top.
Barriers to Pediatric Lead Screening: Implications From a Web-Based Survey of Vermont Pediatricians
Authors: Keeshan Britton , Avener Catherine , Abramson Amanda , Brennan Jillian , Hill Elizabeth , MacLean Jeffrey , Mebust Kelly , Maruti Sanchit , Carney Jan , Davis Wendy , Sumner Austin
Published: February 2010

The pernicious effects of lead on child health are well documented. The Vermont Department of Health (VDH) recommends screening all 12- and 24-month-old children for elevated blood lead levels (BLL). In 2006, only 41.4% of 24-month-old Vermont children were screened. To identify barriers preventing pediatricians from performing blood lead screening, a survey was distributed to Vermont primary care pediatricians—divided in higher and lower screening groups. Vermont pediatricians were more likely to be lower screeners if they reported negative health outcomes began at BLL >" xbd="641" xhg="618" ybd="1456" yhg="1421"/> 10 µg/dL (odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.12-11.99), practiced in Chittenden County (OR = 3.34, 95% CI = 1.14-9.78), or disagreed with the VDH’s recommendation (OR = 4.90, 95% CI = 1.66-15.50). Adjusted analysis indicated the most significant determinants of lower screening rates were male gender, a perceived dangerous BLL as >10 µg/dL and low self-reported Medicaid population. The VDH may have an opportunity to increase BLL screening emphasizing the significant health risks associated with BLL ≤ 10 µg/dL.
Public Services and Women’s Work in Early Modern Dutch Towns
Authors: van der Heijden Manon , Schmidt Ariadne
Published: February 2010

This article analyzes the influence of professionalization and the broader process of bureaucratization on female labor participation in the public service sector in early modern towns in the Dutch province of Holland. Contrary to suggestions in other literature, women were found in a broad range of public offices, and developments in this sector did not lead to the exclusion of women in the course of the early modern period. Women were mainly employed in the lowest level jobs in the sector, and their work was barely affected by professionalization. Furthermore, the strong division of labor along gender lines prevented the exclusion of women. Specialization and diversification of work resulted, instead, in an expansion of employment opportunities, not only for men but also for women.
Metaphor No More: A 15-Year Review of the Team Mental Model Construct
Authors: Mohammed Susan , Ferzandi Lori , Hamilton Katherine
Published: February 2010

Representing one type of team cognition, team mental models (TMMs) are organized mental representations of the key elements within a team’s relevant environment that are shared across team members. Although introduced amid considerable confusion concerning their nature and potential usefulness, there has been a proliferation of published studies over the past decade that have directly measured TMMs using a variety of methodologies and research designs. Capturing these exciting research developments, the purpose of this review was to inventory what has been accomplished thus far and to offer an agenda for the next wave of research. Specifically, we overview the conceptual underpinnings of TMMs, discuss measurement issues, and review the empirical record related to the outcomes, antecedents, and longitudinal work on TMMs. We conclude by highlighting fruitful opportunities for further research.
The UFAIL Approach: Unconventional Technologies and Their “Unintended” Effects
Authors: Agler David W.
Published: February 2010

This essay presents the use-first-and-investigate-later (UFAIL) approach to technological use through two case studies: the atomic bomb in World War II and chemical defoliants during the Vietnam War. The methodology of UFAIL is as follows: despite limited understanding of an array of potential effects (medical, environmental, etc.), technology users employ a commitment to ex post facto investigations of these effects. In generalizing these cases, the essay argues (a) that failure to check rapid technological uptake will result in continued disaster and (b) the abatement of the negative consequences of UFAIL is a more tempered approach to the infiltration of technologies into society by rigorous and preemptive investigation into the potential effects of a technology.
Antigenotoxic effect of mangiferin and changes in antioxidant enzyme levels of Swiss albino mice treated with cadmium chloride
Authors: Kasi Viswanadh E. , Nageshwar Rao B. , Satish Rao BS
Published: February 2010

Cadmium is an environmental metal toxin implicated in human diseases. Mangiferin (MGN), a naturally occurring glucosylxanthone, is present in Mangifera indica. In this study, the protective role of MGN against cadmium chloride (CdCl2)-induced genotoxicity was studied in Swiss albino mice. Mice were administered with single intra-peritoneal (i.p.) optimal dose of MGN (2.5 mg/kg b.wt.) before treatment with various concentrations of CdCl2(7, 8, 9, 10 and 11 mg/kg b.wt.). The LD50(30)was found to be 8.5 mg/kg b.wt. for DDW + CdCl2group, while it was increased to 9.77 mg/kg after MGN treatment resulting in increase in the LD50(30)value by 1.26 mg, with a dose reduction factor (DRF) of 1.14. Treatment of mice to various doses of CdCl2resulted in a dose-dependent increase in the frequency of micronucleated polychromatic (MnPCE) and normochromatic erythrocytes (MnNCE), with corresponding decrease in the polychromatic / normochromatic erythrocyte ratio (PCE/NCE ratio) at various post-treatment times. MGN (2.5 mg/kg b.wt.) pretreatment significantly (p < .001) reduced the frequency of MnPCE, MnNCE and increased PCE/NCE ratio when compared with the DDW + CdCl2group at all post-treatment times indicating its antigenotoxic effect. Further, pretreatment of MGN declined the lipid peroxidation (LPx) content in liver, whereas significant increase was observed in hepatic Glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activity. Our study revealed that MGN has potent antigenotoxic effect against CdCl2-induced toxicity in mice, which may be due to the scavenging of free radicals and increased antioxidant status.
The Impact of the Global Financial Crisis on Emerging and Frontier Markets in Africa
Authors: Boorman Jack , Christensen Benedicte Vibe
Published: February 2010

The financial crisis that has swept through the global economy since the middle of 2007 has led to a sharp deceleration in economic growth in the emerging and frontier market economies in Africa. The record growth performance of gross domestic product of about 6 percent per annum that Africa had experienced during 2002–07 has been seriously interrupted. The consequences on employment and poverty of this interruption could be dire. In the end, the economic impact of the crisis on Africa will depend crucially on the duration and depth of the global recession, the strength of the recovery, the revival of capital markets and foreign investment, and on developments in commodity prices. Ultimately, Africa’s emergence from the crisis will also depend on the policy reactions of the countries that are most seriously affected. Since the transmission channels through which the global crisis is affecting Africa varies significantly across countries, setting common policy guidelines for a group of countries as diverse as the emerging and frontier countries of Africa is impossible. But, policy makers must act! They are faced with the dilemma of responding to the short-term declines on output and rising unemployment that have already occurred, but in an environment of great uncertainty about the future course of the global economy and global financial markets. In this environment, it is important that any short-term responses do not impair medium-term prospects. This paper examines the channels through which countries are being impacted by the crisis, identifies the key policy challenges they are confronting, and makes suggestions for formulating appropriate fiscal policy, dealing with the decline in private remittances and tourism and the likely significantly weaker prospects for foreign direct investment, and for determining the scope for official financing. In general, it is essential that countries continue to pursue policy reforms that will place them in the best possible position to take advantage of the improvement in the global economy when that occurs.
Clinical Usefulness of the Oppositional Defiant Disorder Rating Scale (ODDRS)
Authors: O'Laughlin Elizabeth M. , Hackenberg Jessica L. , Riccardi Maria M.
Published: February 2010

The present study examined the reliability, validity, and clinical utility of the Oppositional Defiant Disorder Rating Scale (ODDRS) in a population of children referred for ADHD evaluation. The diagnostic benefit of using a rating scale specific to Oppositional Defiant Disorder (ODD), in addition to a broad range behavior scale, was also investigated. Parents and teachers of 177 clinic-referred children provided ratings on the ODDRS. The average correlation between parent and teacher ratings was minimal (r = .13). Children diagnosed with ODD through structured parent interviews were found to have elevated scores on the parent version of the ODDRS, as compared to children without a research diagnosis of ODD. However teacher ratings did not discriminate between the ODD and no-ODD groups. There was minimal evidence of incremental validity as classification rates for the ODDRS were almost identical to classification rates based on the Aggression subscale of the Behavior Assessment System for Children (BASC-2).
Review: Electronic Health Records and the Reliability and Validity of Quality Measures: A Review of the Literature
Authors: Chan Kitty S. , Fowles Jinnet B. , Weiner Jonathan P.
Published: February 2010

Previous reviews of research on electronic health record (EHR) data quality have not focused on the needs of quality measurement. The authors reviewed empirical studies of EHR data quality, published from January 2004, with an emphasis on data attributes relevant to quality measurement. Many of the 35 studies reviewed examined multiple aspects of data quality. Sixty-six percent evaluated data accuracy, 57% data completeness, and 23% data comparability. The diversity in data element, study setting, population, health condition, and EHR system studied within this body of literature made drawing specific conclusions regarding EHR data quality challenging. Future research should focus on the quality of data from specific EHR components and important data attributes for quality measurement such as granularity, timeliness, and comparability. Finally, factors associated with poor or variability in data quality need to be better understood and effective interventions developed.
Atorvastatin Combined To Interferon to Verify the Efficacy (ACTIVE) in relapsing— remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy
Authors: Lanzillo Roberta , Orefice Giuseppe , Quarantelli Mario , Rinaldi Carlo , Prinster Anna , Ventrella Gianluca , Spitaleri Daniele , Lus Giacomo , Vacca Giovanni , Carotenuto Barbara , Salvatore Elena , Brunetti Arturo , Tedeschi Gioacchino , Brescia Morra Vincenzo
Published: February 2010

A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing—remitting multiple sclerosis patients, aged 18—50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 µg (three times weekly) for 12 months, were randomized to combination therapy (interferon + atorvastatin 20 mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A ( n = 21) or B ( n = 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline ( p = 0.007) and significantly fewer relapses versus the two pre-randomization years ( p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p = 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone.
Systems, stakeholders, and students: including students in school reform
Authors: Zion Shelley D.
Published: February 2010

The education system in the United States is under pressure from a variety of sources to reform and improve the delivery of educational services to students. Change across a system as complex and dynamic as the educational system requires a systemic approach and requires the participation or buy-in of all participants and stakeholders. This article examines the importance of including students as stakeholders in systemic change efforts. The analysis of this research, framed in the context of including stakeholders in change efforts, will create an opportunity for conversation of ways in which to bring students' voices into school reform.
Environmental Interventions and the Design of Homes for Older Adults With Dementia: An Overview
Authors: van Hoof J. , Kort H.S.M. , van Waarde H. , Blom M.M.
Published: February 2010

In Western societies, the vast majority of people with dementia live at home and wish to remain doing so for as long as possible. Aging in place can be facilitated through a variety of environmental interventions, including home modifications. This article provides an overview of existing design principles and design goals, and environmental interventions implemented at home, based on literature study and additional focus group sessions. There is a multitude of design principles, design goals, and environmental interventions available to assist with activities of daily living and functions, although few systematic studies have been conducted on the efficacy of these goals and interventions. The own home seems to be a largely ignored territory in research and government policies, which implies that many problems concerning aging in place and environmental interventions for dementia are not adequately dealt with.
Integrative Oncology for the Whole Person: A Multidimensional Approach to Cancer Care
Authors: Geffen Jeremy R.
Published: February 2010

Today, more than ever before, millions of people are seeking an approach to medicine and health care that is more comprehensive, more holistic and integrative, and more compassionate and sensitive to their needs as a whole person. This is particularly true for those dealing with cancer. Changing patient demographics, heightened consumer demand for complementary and alternative medicine (CAM) products and services, advances in medical science and technology, expanding access to the Internet and health information, and other factors have contributed to a wave of transformation that is unprecedented in its impact on the entire health care system. These trends have fueled the emerging fields of integrative medicine and oncology, which are growing rapidly. As these fields continue to evolve, they will move beyond the present integrative model to a broader vision of whole-person, multidimensional care that will more fully and coherently address and embrace all dimensions of the human experience. This article describes 6 major driving forces behind the wave of transformation presently under way in medicine and health care. It provides a brief, historical overview of integrative medicine and oncology and summarizes the present status of these emerging fields. It discusses the future of integrative medicine and oncology, including a multidimensional approach to care, and highlights 5 key elements that underlie this approach. Finally, it describes The Seven Levels of Healing — a model of multidimensional care—and concludes with a discussion of 3 important challenges and opportunities for medicine and health care that lie on the horizon.
Where’s My Montage? The Performance of Hard Work and Its Reward in Film, Television, and MMOGs
Authors: Consalvo Mia , Alley Timothy Dodd , Dutton Nathan , Falk Matthew , Fisher Howard , Harper Todd , Yulish Adam
Published: February 2010

Every massively multiplayer online game (MMOG) begins new players at Level 1. The player must grind his or her way through many early levels to reach any kind of decent reward for the hours invested. Compared to films going back to Rocky and television shows such as Crime Scene Investigation (CSI), there is no montage to fast-forward through the work involved in reaching the game’s reward. What is it about online games or the player that makes such work so compelling? Why would hard work, something that is often avoided in the daily grind of an 8—5 job, be forced upon the videogame player—often to his or her delight? To address these questions, we use Ian Bogost’s concept of unit operations to evaluate the concept that ‘‘hard work is rewarded’’ as it relates to various media, including films and videogames, and to analyze the historical and theoretical implications of the concept.
Ulnar Ray Deficiency: a Review of the Classification Systems, the Clinical Features in 72 Cases, and Related Developmental Biology
Authors: Al-Qattan M.M. , Al-Sahabi A. , Al-Arfaj N.
Published: February 2010

Ulnar ray deficiency is rare and has a variable presentation. As a result, there are many different classification systems for this anomaly. Furthermore, the developmental biology of the anomaly is still not fully understood. The aim of this article is to review the previous classification systems, present the clinical features in 72 cases and discuss the developmental biology of ulnar ray deficiency.
Efficacy of the JAK2 inhibitor INCB16562 in a murine model of MPLW515L-induced thrombocytosis and myelofibrosis
Authors: Koppikar Priya , Abdel-Wahab Omar , Hedvat Cyrus , Marubayashi Sachie , Patel Jay , Goel Aviva , Kucine Nicole , Gardner Jeffrey R. , Combs Andrew P. , Vaddi Kris , Haley Patrick J. , Burn Timothy C. , Rupar Mark , Bromberg Jacqueline F. , Heaney Mark L. , de Stanchina Elisa , Fridman Jordan S. , Levine Ross L.
Published: February 2010

The discovery of JAK2 and MPL mutations in patients with myeloproliferative neoplasms (MPNs) provided important insight into the genetic basis of these disorders and led to the development of JAK2 kinase inhibitors for MPN therapy. Although recent studies have shown that JAK2 kinase inhibitors demonstrate efficacy in a JAK2V617F murine bone marrow transplantation model, the effects of JAK2 inhibitors on MPLW515L-mediated myeloproliferation have not been investigated. In this report, we describe the in vitro and in vivo effects of INCB16562, a small-molecule JAK2 inhibitor. INCB16562 inhibited proliferation and signaling in cell lines transformed by JAK2 and MPL mutations. Compared with vehicle treatment, INCB16562 treatment improved survival, normalized white blood cell counts and platelet counts, and markedly reduced extramedullary hematopoeisis and bone marrow fibrosis. We observed inhibition of STAT3 and STAT5 phosphorylation in vivo consistent with potent inhibition of JAK-STAT signaling. These data suggest JAK2 inhibitor therapy may be of value in the treatment of JAK2V617F-negative MPNs. However, we did not observe a decrease in the size of the malignant clone in the bone marrow of treated mice at the end of therapy, which suggests that JAK2 inhibitor therapy, by itself, was not curative in this MPN model.
Development of multilineage adult hematopoiesis in the zebrafish with a runx1 truncation mutation
Authors: Sood Raman , English Milton A. , Belele Christiane L. , Jin Hao , Bishop Kevin , Haskins Rebecca , McKinney Mary Cathleen , Chahal Jagman , Weinstein Brant M. , Wen Zilong , Liu P. Paul
Published: February 2010

Runx1 is required for the emergence of hematopoietic stem cells (HSCs) from hemogenic endothelium during embryogenesis. However, its role in the generation and maintenance of HSCs during adult hematopoiesis remains uncertain. Here, we present analysis of a zebrafish mutant line carrying a truncation mutation, W84X, in runx1. The runx1W84X/W84X embryos showed blockage in the initiation of definitive hematopoiesis, but some embryos were able to recover from a larval “bloodless” phase and develop to fertile adults with multilineage hematopoiesis. Using cd41–green fluorescent protein transgenic zebrafish and lineage tracing, we demonstrated that the runx1W84X/W84X embryos developed cd41+ HSCs in the aorta-gonad-mesonephros region, which later migrated to the kidney, the site of adult hematopoiesis. Overall, our data suggest that in zebrafish adult HSCs can be formed without an intact runx1.
Cigarette smoke enhances β-defensin 2 expression in rat airwaysvianuclear factor-κB activation
Authors: Chen L. , Sun B-B. , Wang T. , Wang X. , Li J-Q. , Wang H-X. , Zhang S-F. , Liu D-S. , Liu L. , Xu D. , Ou X-M. , Chen Y-J. , Yang T. , Zhou H. , Wen F-Q.
Published: February 2010

β-defensin 2 (BD-2), an antimicrobial peptide, participates in airway defence. Cigarette smoke (CS) is a major risk factor for the development of chronic obstructive pulmonary disease. This study mainly aims to investigate the effect of CS on rat BD-2 (rBD-2) expression in rat airways.

Rats were exposed to CS and treated with caffeic acid phenethyl ester (CAPE), a nuclear factor (NF)-κB inhibitor, or astragaloside IV (AS-IV), an active ingredient ofAstragalus mongholicus. Besides the analysis of bronchoalveolar lavage fluid (BALF) and histological changes after CS exposure, rBD-2 expression was investigated with immunohistochemistry, reverse transcription PCR and ELISA. Total glutathione and nitric oxide (NO) levels in rat lungs were also detected.

CS exposure markedly increased rBD-2 immunoreactivity, as well as rBD-2 mRNA and protein levels in rat airways, which were inhibited by CAPE treatment. Moreover, associated airway inflammation induced by CS was demonstrated by histological changes, increased cell counts and pro-inflammatory cytokines in BALF, and NF-κB activation and high levels of total glutathione and NO, which were all reversed by AS-IV in a dose-dependent fashion.

In conclusion, CS exposure induces rBD-2 expression in rat airwaysviaa NF-κB-dependent pathway, and AS-IV attenuates CS-induced airway inflammation due to its anti-inflammatory and antioxidant properties, at least partly through NF-κB inactivation.
Application of a prediction model for work-related sensitisation in bakery workers
Authors: Meijer E. , Suarthana E. , Rooijackers J. , Grobbee D.E. , Jacobs J.H. , Meijster T. , de Monchy J.G.R. , van Otterloo E. , van Rooy F.G.B.G.J. , Spithoven J.J.G. , Zaat V.A.C. , Heederik D.J.J.
Published: February 2010

Identification of work-related allergy, particularly work-related asthma, in a (nationwide) medical surveillance programme among bakery workers requires an effective and efficient strategy.

Bakers at high risk of having work-related allergy were indentified by use of a questionnaire-based prediction model for work-related sensitisation. The questionnaire was applied among 5,325 participating bakers. Sequential diagnostic investigations were performed only in those with an elevated risk. Performance of the model was evaluated in 674 randomly selected bakers who participated in the medical surveillance programme and the validation study. Clinical investigations were evaluated in the first 73 bakers referred at high risk.

Overall 90% of bakers at risk of having asthma could be identified. Individuals at low risk showed 0.3–3.8% work-related respiratory symptoms, medication use or absenteeism. Predicting flour sensitisation by a simple questionnaire and score chart seems more effective at detecting work-related allergy than serology testing followed by clinical investigation in all immunoglobulin E class II-positive individuals.

This prediction based stratification procedure appeared effective in detecting work-related allergy among bakers and can accurately be used for periodic examination, especially in small enterprises where delivery of adequate care is difficult. This approach may contribute to cost reduction.
BMP-2 functions independently of SHH signaling and triggers cell condensation and apoptosis in regenerating axolotl limbs
Authors: Guimond Jean-Charles , Lévesque Mathieu , Michaud Pierre-Luc , Berdugo Jérémie , Finnson Kenneth , Philip Anie , Roy Stéphane
Published: February 2010

Background

Axolotls have the unique ability, among vertebrates, to perfectly regenerate complex body parts, such as limbs, after amputation. In addition, axolotls pattern developing and regenerating autopods from the anterior to posterior axis instead of posterior to anterior like all tetrapods studied to date. Sonic hedgehog is important in establishing this anterior-posterior axis of limbs in all tetrapods including axolotls. Interestingly, its expression is conserved (to the posterior side of limb buds and blastemas) in axolotl limbs as in other tetrapods. It has been suggested that BMP-2 may be the secondary mediator of sonic hedgehog, although there is mounting evidence to the contrary in mice. Since BMP-2 expression is on the anterior portion of developing and regenerating limbs prior to digit patterning, opposite to the expression of sonic hedgehog, we examined whether BMP-2 expression was dependent on sonic hedgehog signaling and whether it affects patterning of the autopod during regeneration.

Results

The expression of BMP-2 and SOX-9 in developing and regenerating axolotl limbs corresponded to the first digits forming in the anterior portion of the autopods. The inhibition of sonic hedgehog signaling with cyclopamine caused hypomorphic limbs (during development and regeneration) but did not affect the expression of BMP-2 and SOX-9. Overexpression of BMP-2 in regenerating limbs caused a loss of digits. Overexpression of Noggin (BMP inhibitor) in regenerating limbs also resulted in a loss of digits. Histological analysis indicated that the loss due to BMP-2 overexpression was the result of increased cell condensation and apoptosis while the loss caused by Noggin was due to a decrease in cell division.

Conclusion

The expression of BMP-2 and its target SOX-9 was independent of sonic hedgehog signaling in developing and regenerating limbs. Their expression correlated with chondrogenesis and the appearance of skeletal elements has described in other tetrapods. Overexpression of BMP-2 did not cause the formation of extra digits, which is consistent with the hypothesis that it is not the secondary signal of sonic hedgehog. However, it did cause the formation of hypomorphic limbs as a result of increased cellular condensation and apoptosis. Taken together, these results suggest that BMP-2 does not have a direct role in patterning regenerating limbs but may be important to trigger condensation prior to ossification and to mediate apoptosis.
Erratum to: 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: February 2010

The version of this article published in BMC Genomics 2009, 10: 558, contains data in Table 1 which are now known to be unreliable, and an illustration, in Figure 1, of unusual miRNA processing events predicted by these unreliable data. In this full-length correction, new data replace those found to be unreliable, leading to a more straightforward interpretation without altering the principle conclusions of the study. Table 1 and associated methods have been corrected, Figure 1 deleted, supplementary file 1 added, and modifications made to the sections "Deep sequencing of small RNAs from grapevine leaf tissue" and "Microarray analysis of miRNA expression". The editors and authors regret the inconvenience caused to readers by premature publication of the original paper.

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.

Conclusions

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.
Polymorphisms in O-methyltransferase genes are associated with stover cell wall digestibility in European maize (Zea maysL.)
Authors: Brenner Everton A , Zein Imad , Chen Yongsheng , Andersen Jeppe R , Wenzel Gerhard , Ouzunova Milena , Eder Joachim , Darnhofer Birte , Frei Uschi , Barrière Yves , Lübberstedt Thomas
Published: February 2010

Background

OMT (O-methyltransferase) genes are involved in lignin biosynthesis, which relates to stover cell wall digestibility. Reduced lignin content is an important determinant of both forage quality and ethanol conversion efficiency of maize stover.

Results

Variation in genomic sequences coding for COMT, CCoAOMT1, and CCoAOMT2 was analyzed in relation to stover cell wall digestibility for a panel of 40 European forage maize inbred lines, and re-analyzed for a panel of 34 lines from a published French study. Different methodologies for association analysis were performed and compared. Across association methodologies, a total number of 25, 12, 1, 6 COMT polymorphic sites were significantly associated with DNDF, OMD, NDF, and WSC, respectively. Association analysis for CCoAOMT1 and CCoAOMT2 identified substantially fewer polymorphic sites (3 and 2, respectively) associated with the investigated traits. Our re-analysis on the 34 lines from a published French dataset identified 14 polymorphic sites significantly associated with cell wall digestibility, two of them were consistent with our study. Promising polymorphisms putatively causally associated with variability of cell wall digestibility were inferred from the total number of significantly associated SNPs/Indels.

Conclusions

Several polymorphic sites for three O-methyltransferase loci were associated with stover cell wall digestibility. All three tested genes seem to be involved in controlling DNDF, in particular COMT. Thus, considerable variation among Bm3 wildtype alleles can be exploited for improving cell-wall digestibility. Target sites for functional markers were identified enabling development of efficient marker-based selection strategies.
Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer
Authors: Lum Amy M , Wang Bruce B , Beck-Engeser Gabriele B , Li Lauri , Channa Namitha , Wabl Matthias
Published: February 2010

Background

GPR110 is an orphan G protein-coupled receptor--a receptor without a known ligand, a known signaling pathway, or a known function. Despite the lack of information, one can assume that orphan receptors have important biological roles. In a retroviral insertion mutagenesis screen in the mouse, we identified GPR110 as an oncogene. This prompted us to study the potential isoforms that can be gleaned from known GPR110 transcripts, and the expression of these isoforms in normal and transformed human tissues.

Methods

Various epitope-tagged isoforms of GPR110 were expressed in cell lines and assayed by western blotting to determine cleavage, surface localization, and secretion patterns. GPR110 transcript and protein levels were measured in lung and prostate cancer cell lines and clinical samples, respectively, by quantitative PCR and immunohistochemistry.

Results

We found four potential splice variants of GPR110. Of these variants, we confirmed three as being expressed as proteins on the cell surface. Isoform 1 is the canonical form, with a molecular mass of about 100 kD. Isoforms 2 and 3 are truncated products of isoform 1, and are 25 and 23 kD, respectively. These truncated isoforms lack the seven-span transmembrane domain characteristic of GPR proteins and thus are not likely to be membrane anchored; indeed, isoform 2 can be secreted. Compared with the median gene expression of ~200 selected genes, GPR110 expression was low in most tissues. However, it had higher than average gene expression in normal kidney tissue and in prostate tissues originating from older donors. Although identified as an oncogene in murine T lymphomas, GPR110 is greatly overexpressed in human lung and prostate cancers. As detected by immunohistochemistry, GPR110 was overexpressed in 20 of 27 (74%) lung adenocarcinoma tissue cores and in 17 of 29 (59%) prostate adenocarcinoma tissue cores. Additionally, staining with a GPR110 antibody enabled us to differentiate between benign prostate hyperplasia and potential incipient malignancy.

Conclusion

Our work suggests a role for GPR110 in tumor physiology and supports it as a potential therapeutic candidate and disease marker for both lung and prostate cancer.
Non-rigid registration of breast surfaces using the laplace and diffusion equations
Authors: Ong Rowena E , Ou Jao J , Miga Michael I
Published: February 2010

A semi-automated, non-rigid breast surface registration method is presented that involves solving the Laplace or diffusion equations over undeformed and deformed breast surfaces. The resulting potential energy fields and isocontours are used to establish surface correspondence. This novel surface-based method, which does not require intensity images, anatomical landmarks, or fiducials, is compared to a gold standard of thin-plate spline (TPS) interpolation. Realistic finite element simulations of breast compression and further testing against a tissue-mimicking phantom demonstrate that this method is capable of registering surfaces experiencing 6 - 36 mm compression to within a mean error of 0.5 - 5.7 mm.
Smart density: a more accurate method of measuring rural residential density for health-related research
Authors: Owens Peter M , Titus-Ernstoff Linda , Gibson Lucinda , Beach Michael L , Beauregard Sandy , Dalton Madeline A
Published: February 2010

Background

Studies involving the built environment have typically relied on US Census data to measure residential density. However, census geographic units are often unsuited to health-related research, especially in rural areas where development is clustered and discontinuous.

Objective

We evaluated the accuracy of both standard census methods and alternative GIS-based methods to measure rural density.

Methods

We compared residential density (units/acre) in 335 Vermont school neighborhoods using conventional census geographic units (tract, block group and block) with two GIS buffer measures: a 1-kilometer (km) circle around the school and a 1-km circle intersected with a 100-meter (m) road-network buffer. The accuracy of each method was validated against the actual residential density for each neighborhood based on the Vermont e911 database, which provides an exact geo-location for all residential structures in the state.

Results

Standard census measures underestimate residential density in rural areas. In addition, the degree of error is inconsistent so even the relative rank of neighborhood densities varies across census measures. Census measures explain only 61% to 66% of the variation in actual residential density. In contrast, GIS buffer measures explain approximately 90% of the variation. Combining a 1-km circle with a road-network buffer provides the closest approximation of actual residential density.

Conclusion

Residential density based on census units can mask clusters of development in rural areas and distort associations between residential density and health-related behaviors and outcomes. GIS-defined buffers, including a 1-km circle and a road-network buffer, can be used in conjunction with census data to obtain a more accurate measure of residential density.