bluuebunny/crossref_metadata_2025 huggingface dataset:
Medial Knee Pain in a Runner
Authors: Johar Sandeep K.
Published: June 2010

A 41-year-old female runner presented to the sports medicine clinic for evaluation of bilateral medial knee pain, left greater than right. Physical examination demonstrated tenderness to palpation over the central aspect of the medial collateral ligament. Anteroposterior and lateral standing knee films were unremarkable. The patient received a corticosteroid injection over the tibial collateral ligament bursa with resolution of symptoms within 2 weeks. There have been few documented case reports of this type of injury in patients with knee pain. Prompt diagnosis and appropriate definitive treatment are important to establish to provide maximum recovery and minimize long-term disability, which may include chronic refractory pain during aggravating activities.
Pregnancy and fetal outcomes of symptoms of sleep-disordered breathing
Authors: Bourjeily G. , Raker C.A. , Chalhoub M. , Miller M.A.
Published: June 2010

The physiological changes of pregnancy may predispose females to develop sleep-disordered breathing (SDB) or protect against it. Studies evaluating outcomes of SDB symptoms in pregnancy are scarce. The goal of this study was to evaluate the prevalence of SDB symptoms in pregnancy and their relationship with pregnancy and neonatal outcomes.

A cross-sectional survey of randomly selected immediate postpartum females was performed using the multivariable apnoea prediction index. Record review, including demographics and medical history, was performed. Main outcome measures included pregnancy and neonatal outcomes.

1,000 subjects were recruited. Mean±sdage was 29.1±6.1 yrs. Factors used in the regression analysis included age, body mass index, diabetes, chronic hypertension, multifetal gestations, smoking and renal disease. Snoring was present in 35.1% of subjects. Symptoms of SDB were associated with a higher likelihood of pregnancy-induced hypertension and pre-eclampsia (adjusted OR 2.3, 95% CI 1.4–4.0), gestational diabetes (adjusted OR 2.1, 95% CI 1.3–3.4) and unplanned Caesarean deliveries (adjusted OR 2.1, 95% CI 1.4–3.2) after multivariable regression analysis. Gasping may have been associated with a higher likelihood of preterm delivery, after adjusting for age and multifetal pregnancies (adjusted OR 1.8, 95% CI 1.1–3.2) but this association appeared to be mediated by pre-eclampsia.

Symptoms of SDB are common in pregnancy and associated with a higher likelihood of gestational hypertensive disorders, gestational diabetes and unplanned Caesarean deliveries.
Inhaled drugs as risk factors for community-acquired pneumonia
Authors: Almirall J. , Bolíbar I. , Serra-Prat M. , Palomera E. , Roig J. , Hospital I. , Carandell E. , Agustí M. , Ayuso P. , Estela A. , Torres A.
Published: June 2010

The effect of inhaled drugs in community-acquired pneumonia (CAP) is unclear. This case–control study was designed to determine whether inhaled drugs were risk factors for CAP.

All incident cases of confirmed CAP that occurred over 1 yr in patients with chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD) or asthma were included, as well as CB, COPD and asthma controls. Risk factors for CAP and inhaled treatment were recorded during a personal interview.

An effect of inhaled drugs on the risk of CAP was observed in COPD and asthma patients after adjusting for the effect of other respiratory diseases and their concomitant treatments. In COPD patients, inhaled steroids had a risk OR of 3.26 (95% CI 1.07–9.98) and in asthma patients inhaled anticholinergics had a risk OR of 8.80 (95% CI 1.02–75.7). In CB patients, no association with CAP was observed for any inhaler. These effects were independent of adjusting variables related to severity and other respiratory and non-respiratory risk factors for CAP, including vaccines. Inhaled β2-adrenergic agonists did not show a significant effect on the risk of CAP in any of the respiratory diseases.

Inhaled steroids may favour CAP in COPD patients, whereas anticholinergics may favour CAP in asthma patients. It is difficult to differentiate the effect of inhaled therapy from the effect of COPD or asthma severity on the risk of CAP, and these relationships may not be causal, but could call attention to inhaled therapy in COPD and asthma patients.
Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension
Authors: Nikam V.S. , Schermuly R.T. , Dumitrascu R. , Weissmann N. , Kwapiszewska G. , Morrell N. , Klepetko W. , Fink L. , Seeger W. , Voswinckel R.
Published: June 2010

A unique subpopulation of peripheral blood mononuclear cells that exhibit a parallel expression of haematopoietic and mesenchymal markers has been described as “circulating fibrocytes”. These cells were demonstrated to obtain a fibroblastic phenotype in tissues or cell culture and contribute to pulmonary fibrotic disorders and tissue remodelling processes.

The aim of our study was to characterise the recruitment of circulating fibrocytesin vivoin the model of chronic hypoxic pulmonary hypertension in mice and to analyse the therapeutic effect of the stable prostacyclin analogue trepostinil with respect to this cell population.

To track circulating fibrocytesin vivo, we transplanted wild-type mice with bone marrow from ubiquitously eGFP expressing mice and subjected them to chronic hypoxia. We observed significantly increased recruitment of circulating fibrocytes to the remodelled pulmonary resistance arteries in response to hypoxia. Treatment with treprostinil significantly reduced the recruitment of these cells compared to normoxic mice. Treprostinil also reduced right ventricular systolic pressure and slightly reduced the vascular remodelling but failed to reverse the right ventricular hypertrophy.

In summary, we show that circulating fibrocytes contribute to hypoxic pulmonary vascular remodelling and may be specifically targeted by a prostacyclin analogue. Further investigations of cellular and paracrine mechanisms are warranted to decipher their role in pulmonary hypertension.
Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial
Authors: Van Schil P.E. , Baas P. , Gaafar R. , Maat A.P. , Van de Pol M. , Hasan B. , Klomp H.M. , Abdelrahman A.M. , Welch J. , van Meerbeeck J.P.
Published: June 2010

The European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant pleural mesothelioma (with a severity of cT3N1M0 or less).

Induction chemotherapy consisted of three courses of cisplatin 75 mg·m−2and pemetrexed 500 mg·m−2. Nonprogressing patients underwent extrapleural pneumonectomy followed by post-operative radiotherapy (54 Gy, 30 fractions). Our primary end-point was “success of treatment” and our secondary end-points were toxicity, and overall and progression-free survival.

59 patients were registered, one of whom was ineligible. Subjects’ median age was 57 yrs. The subjects’ TNM scores were as follows: cT1, T2 and T3, 36, 16 and six patients, respectively; cN0 and N1, 57 and one patient, respectively. 55 (93%) patients received three cycles of chemotherapy with only mild toxicity. 46 (79%) patients received surgery and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Post-operative radiotherapy was completed in 37 (65%) patients. Grade 3–4 toxicity persisted after 90 days in three (5.3%) patients. Median overall survival time was 18.4 months (95% CI 15.6–32.9) and median progression-free survival was 13.9 months (95% CI 10.9–17.2). Only 24 (42%) patients met the definition of success (one-sided 90% CI 0.36–1.00).

Although feasible, trimodality therapy in patients with mesothelioma was not completed within the strictly defined timelines of this protocol and adjustments are necessary.
TB or not TB: update from the ERS Respiratory Infection Assembly 10
Authors: Miravitlles M. , Ferrara G. , Lange C. , Dimopoulos G. , Rohde G. , Blasi F. , Migliori G.B.
Published: June 2010

Lower respiratory tract infections and tuberculosis represent some of the top health priorities in Europe. In the present report, the most recent advances in the field of disease control, clinical research and basic science of lower respiratory tract infections and tuberculosis are presented through analysis of some of the best abstracts presented at the 19th European Respiratory Society Congress in Vienna (Austria).

Pathogenesis, diagnosis, treatment, prognostic factors and novel diagnostic techniques relevant for bacterial and viral infections, as well as new tools for the diagnosis of latent and active tuberculosis in different sub-groups of patients, are discussed. The growing epidemiological threat represented by multidrug-resistant and extensively drug-resistant tuberculosis cases is presented and its impact analysed.
Association of COPD candidate genes with computed tomography emphysema and airway phenotypes in severe COPD
Authors: Kim W.J. , Hoffman E. , Reilly J. , Hersh C. , DeMeo D. , Washko G. , Silverman E.K.
Published: June 2010

The principal determining factors influencing the development of the airway disease and emphysema components of chronic obstructive pulmonary disease (COPD) have not been clearly defined. Genetic variability in COPD patients might influence the varying degrees of involvement of airway disease and emphysema. Therefore, we investigated the genetic association of single nucleotide polymorphisms (SNPs) in COPD candidate genes for association with emphysema severity and airway wall thickness phenotypes.

Polymorphisms in six candidate genes were analysed in 379 subjects of the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study with quantitative chest computed tomography (CT) data. Genetic association with per cent of lung area below -950 HU (LAA950), airway wall thickness, and derived square root wall area (SRWA) of 10-mm internal perimeter airways were investigated.

Three SNPs inEPHX1, five SNPs inSERPINE2and one SNP inGSTP1were significantly associated with LAA950. Five SNPs inTGFB1, two SNPs inEPHX1, one SNP inSERPINE2and two SNPs inADRB2were associated with airway wall phenotypes in NETT.

In conclusion, several COPD candidate genes showed evidence for association with airway wall thickness and emphysema severity using CT in a severe COPD population. Further investigation will be required to replicate these genetic associations for emphysema and airway wall phenotypes.
Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways
Authors: Cortijo J. , Mata M. , Milara J. , Donet E. , Gavaldà A. , Miralpeix M. , Morcillo E.J.
Published: June 2010

Mucus hypersecretion and mucin MUC5AC overexpression are pathological features of chronic obstructive pulmonary disease (COPD). This study examines the inhibitory effect of aclidinium, a new long-acting muscarinic antagonist, on MUC5AC expression in human airway epithelial cells.

MUC5AC mRNA (RT-PCR) and protein expression (ELISA and immunohistochemistry) were studied in human bronchial tissue and differentiated human airway epithelial cells activated with carbachol (100 μM) or cigarette smoke extract in the absence or presence of aclidinium.

Carbachol increased MUC5AC mRNA and protein expression in human bronchus and cultured epithelial cells. Aclidinium inhibited the carbachol-induced MUC5AC mRNA and protein expression with potency (half maximal inhibitory concentration) ∼1 nM in human bronchus and cultured airway epithelial cells. AG1478, a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, inhibited carbachol-induced MUC5AC responses, indicating EGFR transactivation. Aclidinium inhibited carbachol-induced phospho-EGFR and phospho-p44/42 MAPK expression. In cultured airway epithelial cells transfected with small interfering (si)RNA against muscarinic receptor subtypes, siRNA-M3 but not siRNA-M2 blocked carbachol-induced MUC5AC expression. Cigarette smoke-induced MUC5AC upregulation in cultured airway epithelial cells was suppressed by aclidinium.

In conclusion, aclidinium decreases carbachol and tobacco smoke-induced MUC5AC overexpression in human airway epithelial cells. This effect may contribute to the clinical efficacy of aclidinium in mucus hypersecretory diseases including COPD.
Significant increase of CD57+cells in pulmonary lymphoid follicles of COPD patients
Authors: Olloquequi J. , Montes J.F. , Prats A. , Rodríguez E. , Montero M.A. , García-Valero J. , Ferrer J.
Published: June 2010

Although the presence of pulmonary lymphoid follicles (LFs) has been associated with the progression of chronic obstructive pulmonary disease (COPD), there is no information regarding the pattern of vascularisation, expression of addressins or inflammatory cell densities within these structures in COPD.

Histological and immunohistochemical techniques were used to assess the prevalence, structure, localisation, vascularisation and cell proliferation/apoptosis of LFs, as well as the follicular density of B- and T-lymphocytes, macrophages, dendritic cells and CD57+cells, in lung tissue of nine nonsmokers, 18 smokers without COPD, 16 smokers with moderate COPD and 16 patients with very severe COPD.

The density of CD57+cells within LFs of COPD patients was significantly increased compared to that of nonsmokers and smokers without COPD (p<0.05). Moreover, the percentage of LF profiles with cell apoptosis was also significantly higher in COPD patients (p = 0.03). By contrast, no significant differences among groups were observed in the follicular densities of other inflammatory cells, nor in the distribution of blood and lymphatic vessels within LFs.

Since CD57+cells are important effectors of cytotoxicity and immune regulation, an increase in their follicular density supports the hypothesis of local immune dysfunction in COPD.
14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans
Authors: Tamisier R. , Pépin J.L. , Rémy J. , Baguet J.P. , Taylor J.A. , Weiss J.W. , Lévy P.
Published: June 2010

Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms.

We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean±sdMSNA increased across the exposure (17.2±5.1versus21.7±7.3 bursts·min−1; p<0.01) and baroreflex control of sympathetic outflow declined from -965.3±375.1 to -598.4±162.6 AIU·min−1·mmHg−1(p<0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers.

These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.
Beyond rotamers: a generative, probabilistic model of side chains in proteins
Authors: Harder Tim , Boomsma Wouter , Paluszewski Martin , Frellsen Jes , Johansson Kristoffer E , Hamelryck Thomas
Published: June 2010

Background

Accurately covering the conformational space of amino acid side chains is essential for important applications such as protein design, docking and high resolution structure prediction. Today, the most common way to capture this conformational space is through rotamer libraries - discrete collections of side chain conformations derived from experimentally determined protein structures. The discretization can be exploited to efficiently search the conformational space. However, discretizing this naturally continuous space comes at the cost of losing detailed information that is crucial for certain applications. For example, rigorously combining rotamers with physical force fields is associated with numerous problems.

Results

In this work we present BASILISK: a generative, probabilistic model of the conformational space of side chains that makes it possible to sample in continuous space. In addition, sampling can be conditional upon the protein's detailed backbone conformation, again in continuous space - without involving discretization.

Conclusions

A careful analysis of the model and a comparison with various rotamer libraries indicates that the model forms an excellent, fully continuous model of side chain conformational space. We also illustrate how the model can be used for rigorous, unbiased sampling with a physical force field, and how it improves side chain prediction when used as a pseudo-energy term. In conclusion, BASILISK is an important step forward on the way to a rigorous probabilistic description of protein structure in continuous space and in atomic detail.
FunctSNP: an R package to link SNPs to functional knowledge and dbAutoMaker: a suite of Perl scripts to build SNP databases
Authors: Goodswen Stephen J , Gondro Cedric , Watson-Haigh Nathan S , Kadarmideen Haja N
Published: June 2010

Background

Whole genome association studies using highly dense single nucleotide polymorphisms (SNPs) are a set of methods to identify DNA markers associated with variation in a particular complex trait of interest. One of the main outcomes from these studies is a subset of statistically significant SNPs. Finding the potential biological functions of such SNPs can be an important step towards further use in human and agricultural populations (e.g., for identifying genes related to susceptibility to complex diseases or genes playing key roles in development or performance). The current challenge is that the information holding the clues to SNP functions is distributed across many different databases. Efficient bioinformatics tools are therefore needed to seamlessly integrate up-to-date functional information on SNPs. Many web services have arisen to meet the challenge but most work only within the framework of human medical research. Although we acknowledge the importance of human research, we identify there is a need for SNP annotation tools for other organisms.

Description

We introduce an R package called FunctSNP, which is the user interface to custom built species-specific databases. The local relational databases contain SNP data together with functional annotations extracted from online resources. FunctSNP provides a unified bioinformatics resource to link SNPs with functional knowledge (e.g., genes, pathways, ontologies). We also introduce dbAutoMaker, a suite of Perl scripts, which can be scheduled to run periodically to automatically create/update the customised SNP databases. We illustrate the use of FunctSNP with a livestock example, but the approach and software tools presented here can be applied also to human and other organisms.

Conclusions

Finding the potential functional significance of SNPs is important when further using the outcomes from whole genome association studies. FunctSNP is unique in that it is the only R package that links SNPs to functional annotation. FunctSNP interfaces to local SNP customised databases which can be built for any species contained in the National Center for Biotechnology Information dbSNP database.
Functional genomics of human bronchial epithelial cells directly interacting with conidia of Aspergillus fumigatus
Authors: Gomez Pol , Hackett Tillie L , Moore Margo M , Knight Darryl A , Tebbutt Scott J
Published: June 2010

Background

Aspergillus fumigatus (A. fumigatus)is a ubiquitous fungus which reproduces asexually by releasing abundant airborne conidia (spores), which are easily respirable. In allergic and immunocompromised individualsA. fumigatuscan cause a wide spectrum of diseases, including allergic bronchopulmonary aspergillosis, aspergilloma and invasive aspergillosis. Previous studies have demonstrated thatA. fumigatusconidia are internalized by macrophages and lung epithelial cells; however the exact transcriptional responses of airway epithelial cells to conidia are currently unknown. Thus, the aim of this study was to determine the transcriptomic response of the human bronchial epithelial cell line (16HBE14o-) following interaction withA. fumigatusconidia. We used fluorescence-activated cell sorting (FACS) to separate 16HBE14o- cells having bound and/or internalizedA. fumigatusconidia expressing green fluorescent protein from cells without spores. Total RNA was then isolated and the transcriptome of 16HBE14o- cells was evaluated using Agilent Whole Human Genome microarrays.

Results

Immunofluorescent staining and nystatin protection assays demonstrated that 16HBE14o- cells internalized 30-50% of bound conidia within six hrs of co-incubation. After FAC-sorting of the same cell culture to separate cells associated with conidia from those without conidia, genome-wide analysis revealed a set of 889 genes showing differential expression in cells with conidia. Specifically, these 16HBE14o- cells had increased levels of transcripts from genes associated with repair and inflammatory processes (e.g., matrix metalloproteinases, chemokines, and glutathione S-transferase). In addition, the differentially expressed genes were significantly enriched for Gene Ontology terms including: chromatin assembly, G-protein-coupled receptor binding, chemokine activity, and glutathione metabolic process (up-regulated); cell cycle phase, mitosis, and intracellular organelle (down-regulated).

Conclusions

We demonstrate a methodology using FACs for analyzing the transcriptome of infected and uninfected cells from the same cell population that will provide a framework for future characterization of the specific interactions between pathogens such asA. fumigatuswith human cells derived from individuals with or without underlying disease susceptibility.
In vitro and in vivo comparison of the anti-staphylococcal efficacy of generic products and the innovator of oxacillin
Authors: Rodriguez Carlos A , Agudelo Maria , Zuluaga Andres F , Vesga Omar
Published: June 2010

Background

Oxacillin continues to be an important agent in the treatment of staphylococcal infections; many generic products are available and the only requirement for their approval is demonstration of pharmaceutical equivalence. We tested the assumption that pharmaceutical equivalence predicts therapeutic equivalence by comparing 11 generics with the innovator product in terms of concentration of the active pharmaceutical ingredient (API), minimal inhibitory (MIC) and bactericidal concentrations (MBC), and antibacterial efficacy in the neutropenic mouse thigh infection model.

Methods

The API in each product was measured by a validated microbiological assay and compared by slope (potency) and intercept (concentration) analysis of linear regressions. MIC and MBC were determined by broth microdilution according to Clinical and Laboratory Standard Institute (CLSI) guidelines. For in vivo efficacy, neutropenic ICR mice were inoculated with a clinical strain ofStaphylococcus aureus. The animals had 4.14 ± 0.18 log10CFU/thigh when treatment started. Groups of 10 mice per product received a total dose ranging from 2.93 to 750 mg/kg per day administered q1h. Sigmoidal dose-response curves were generated by nonlinear regression fitted to Hill equation to compute maximum effect (Emax), slope (N), and the effective dose reaching 50% of the Emax(ED50). Based on these results, bacteriostatic dose (BD) and dose needed to kill the first log of bacteria (1LKD) were also determined.

Results

4 generic products failed pharmaceutical equivalence due to significant differences in potency; however, all products were undistinguishable from the innovator in terms of MIC and MBC. Independently of their status with respect to pharmaceutical equivalence or in vitro activity, all generics failed therapeutic equivalence in vivo, displaying significantly lower Emaxand requiring greater BD and 1LKD, or fitting to a non-sigmoidal model.

Conclusions

Pharmaceutical or in vitro equivalence did not entail therapeutic equivalence for oxacillin generic products, indicating that criteria for approval deserve review to include evaluation of in vivo efficacy.
Depression diagnoses following the identification of bipolar disorder: costly incongruent diagnoses
Authors: Stensland Michael D , Schultz Jennifer F , Frytak Jennifer R
Published: June 2010

Background

Previous research has documented that the symptoms of bipolar disorder are often mistaken for unipolar depression prior to a patient's first bipolar diagnosis. The assumption has been that once a patient receives a bipolar diagnosis they will no longer be given a misdiagnosis of depression. The objectives of this study were 1) to assess the rate of subsequent unipolar depression diagnosis in individuals with a history of bipolar disorder and 2) to assess the increased cost associated with this potential misdiagnosis.

Methods

This study utilized a retrospective cohort design using administrative claims data from 2002 and 2003. Patient inclusion criteria for the study were 1) at least 2 bipolar diagnoses in 2002, 2) continuous enrollment during 2002 and 2003, 3) a pharmacy benefit, and 4) age 18 to 64. Patients with at least 2 unipolar depression diagnoses in 2003 were categorized as having an incongruent diagnosis of unipolar depression. We used propensity scoring to control for selection bias. Utilization was evaluated using negative binomial models. We evaluated cost differences between patient cohorts using generalized linear models.

Results

Of the 7981 patients who met all inclusion criteria for the analysis, 17.5% (1400) had an incongruent depression diagnosis (IDD). After controlling for background differences, individuals who received an IDD had higher rates of inpatient and outpatient psychiatric utilization and cost, on average, an additional $1641 per year compared to individuals without an IDD.

Conclusions

A strikingly high proportion of bipolar patients are given the differential diagnosis of unipolar depression after being identified as having bipolar disorder. Individuals with an IDD had increased acute psychiatric care services, suggesting higher levels of relapses, and were at risk for inappropriate treatment, as antidepressant therapy without a concomitant mood-stabilizing medication is contraindicated in bipolar disorder. Further prospective research is needed to validate the findings from this retrospective administrative claims-based analysis.
Applications and methods utilizing the Simple Semantic Web Architecture and Protocol (SSWAP) for bioinformatics resource discovery and disparate data and service integration
Authors: Nelson Rex T , Avraham Shulamit , Shoemaker Randy C , May Gregory D , Ware Doreen , Gessler Damian DG
Published: June 2010

Background

Scientific data integration and computational service discovery are challenges for the bioinformatic community. This process is made more difficult by the separate and independent construction of biological databases, which makes the exchange of data between information resources difficult and labor intensive. A recently described semantic web protocol, the Simple Semantic Web Architecture and Protocol (SSWAP; pronounced "swap") offers the ability to describe data and services in a semantically meaningful way. We report how three major information resources (Gramene, SoyBase and the Legume Information System [LIS]) used SSWAP to semantically describe selected data and web services.

Methods

We selected high-priority Quantitative Trait Locus (QTL), genomic mapping, trait, phenotypic, and sequence data and associated services such as BLAST for publication, data retrieval, and service invocation via semantic web services. Data and services were mapped to concepts and categories as implemented in legacy and de novo community ontologies. We used SSWAP to express these offerings in OWL Web Ontology Language (OWL), Resource Description Framework (RDF) and eXtensible Markup Language (XML) documents, which are appropriate for their semantic discovery and retrieval. We implemented SSWAP services to respond to web queries and return data. These services are registered with the SSWAP Discovery Server and are available for semantic discovery at http://sswap.info.

Results

A total of ten services delivering QTL information from Gramene were created. From SoyBase, we created six services delivering information about soybean QTLs, and seven services delivering genetic locus information. For LIS we constructed three services, two of which allow the retrieval of DNA and RNA FASTA sequences with the third service providing nucleic acid sequence comparison capability (BLAST).

Conclusions

The need for semantic integration technologies has preceded available solutions. We report the feasibility of mapping high priority data from local, independent, idiosyncratic data schemas to common shared concepts as implemented in web-accessible ontologies. These mappings are then amenable for use in semantic web services. Our implementation of approximately two dozen services means that biological data at three large information resources (Gramene, SoyBase, and LIS) is available for programmatic access, semantic searching, and enhanced interaction between the separate missions of these resources.
Anterior gradient-2 plays a critical role in breast cancer cell growth and survival by modulating cyclin D1, estrogen receptor-α and survivin
Authors: Vanderlaag Kathryn E , Hudak Susan , Bald Laura , Fayadat-Dilman Laurence , Sathe Manjiri , Grein Jeff , Janatpour Mary J
Published: June 2010

Introduction

Anterior-gradient 2 (AGR2) is an estrogen-responsive secreted protein. Its upregulation has been well documented in a number of cancers, particularly breast cancer, for which mixed data exist on the prognostic implications of AGR2 expression. Although emerging evidence indicates that AGR2 is associated with poor prognosis, its function and impact on cancer-relevant pathways have not been elucidated in breast cancer.

Methods

To investigate the biologic role of AGR2 in breast cancer, AGR2 was transiently knocked down, by using siRNA, in T47 D and ZR-75-1 (estrogen receptor-α (ER)-positive) and MDA-MB-231 and SK-BR-3 (ER-negative) human breast cancer cell lines. The impact of silencing AGR2 was evaluated in both anchorage-dependent and anchorage-independent growth (soft agar, spheroid) assays. Cell-cycle profiles in ER-positive cell lines were determined with BrdU incorporation, and cell death was measured with Annexin V, JC-1, and F7-26 staining. After transiently silencing AGR2 or stimulating with recombinant AGR2, modulation of key regulators of growth and survival pathways was assessed with Western blot. Combination studies of AGR2 knockdown with the antiestrogens tamoxifen and fulvestrant were carried out and assessed at the level of anchorage-dependent growth inhibition and target modulation (cyclin D1, ER).

Results

AGR2 knockdown inhibited growth in anchorage-dependent and anchorage-independent assays, with a more-pronounced effect in ER-positive cell lines. Cyclin D1 levels and BrdU incorporation were reduced with AGR2 knockdown. Conversely, cyclin D1 was induced with recombinant AGR2. AGR2 knockdown induced cell death in ZR-75-1 and T47 D cells, and also downregulated survivin and c-Myc. Evidence of AGR2-ER crosstalk was demonstrated by a reduction of ER at the protein level after transiently silencing AGR2. AGR2 knockdown in combination with fulvestrant or tamoxifen did not preclude the efficacy of the antiestrogens, but enhanced it. In addition, p-Src, implicated in tamoxifen resistance, was downregulated with AGR2 knockdown.

Conclusions

Transiently silencing AGR2 in ER-positive breast cancer cell lines inhibited cell growth and cell-cycle progression and induced cell death. Breast cancer drivers (ER and cyclin D1) as well as cancer-signaling nodes (pSrc, c-Myc, and survivin) were demonstrated to be downstream of AGR2. Collectively, the data presented support the utility of anti-AGR2 therapy in ER-positive breast cancers because of its impact on cancer-relevant pathways.
A Spreadsheet Scenario Analysis Technique That Integrates with Optimization and Simulation
Authors: Grossman Thomas A. , Özlük Özgür
Published: June 2010

Scenario analysis is a widely used technique, and business students should be proficient in running scenarios through a spreadsheet model. We propose 10 desirable properties for a scenario analysis technique, and show that the Microsoft Excel Scenario Manager tool satisfies only one of them. We provide a tutorial for a better technique that can be programmed into an existing spreadsheet in a matter of minutes. We show how to integrate the technique with the Excel Solver to allow for rapid optimization of multiple scenarios and with the Crystal Ball add-in for Monte Carlo simulation to enable simulation of multiple scenarios. Our undergraduate and MBA students are able to learn the technique with little difficulty.
Introducing Optimization Techniques to Students: An Exam Case Distribution Model
Authors: Vanhoucke Mario
Published: June 2010

In this paper, an integer programming (IP) model is presented to assign MBA and undergraduate students to groups to solve an exam case in an operations research (O.R.) course. It is assumed that the students have a basic understanding of mathematical programming and are now ready to build their first real-life model in class. Thanks to the direct link with the student's situation and the immediate repercussion on the exam assignment, students can quickly understand the problem and are willing to help to define the problem in class. The example illustrates many O.R.-related issues, such as the balance between problem complexity and solution quality, and the need for dynamic rather than static models. Thanks to its simplicity and practicality, this exercise is an ideal tool to make the often complex domain of O.R. more accessible.
Highlight: Molecular Neurobiology
Authors: Thiel Gerald
Published: June 2010

No abstract available
Insulin receptor substrate 1 regulates the cellular differentiation and the matrix metallopeptidase expression of preosteoblastic cells
Authors: Bu Yan-Hong , He Yu-Ling , Zhou Hou-De , Liu Wei , Peng Dan , Tang Ai-Guo , Tang Ling-Li , Xie Hui , Huang Qiu-Xia , Luo Xiang-Hang , Liao Er-Yuan
Published: June 2010

Insulin receptor substrate 1 (IRS1) is an essential molecule for the intracellular signaling of IGF1 and insulin, which are potent anabolic regulators of bone metabolism. Osteoblastic IRS1 is essential for maintaining bone turnover; however, the mechanism underlying this regulation remains unclear. To clarify the role of IRS1 in bone metabolism, we employed RNA interference to inhibit IRS1 gene expression and observed the effects of silencing this gene on the proliferation and differentiation of and the expression of matrix metallopeptidase (MMP) and tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) in MC3T3-E1 cells. Our results showed that IRS1 short hairpin RNAs can effectively suppress the expression of IRS1, and inhibit the phosphorylation of AKT in IRS1 pathway; reduce the expression of MMP2, MMP3, MMP13, and MMP14, decrease the expression of TNFRSF11B and RANKL (also known as tumor necrosis factor (ligand) superfamily, member 11), however increase the RANKL/TNFRSF11B ratio; decrease cell survival, proliferation, and mineralization, and impair the differentiation of MC3T3-E1 cells. The downregulation of IRS1 had no effect on the expression of MMP1. Our findings suggest that IRS1 not only promotes bone formation and mineralization but also might play roles in bone resorption partly via the regulation of MMPs and RANKL/TNFRSF11B ratio, thus regulates the bone turnover.
Potential of Wild Yellow Lupin from Northwestern Spain
Authors: Lema M. , Lindner R.
Published: June 2010

Wild yellow lupin (Lupinus luteus L.) is one of the three species of the genus Lupinus that grows naturally in Galicia (northwestern Spain). In this dairy region imported lupin is widely used as a cheap plant‐derived protein for livestock feed. Our objectives were to investigate variation in yellow lupin accessions from northwestern Spain, determine the relationships among them, and identify useful accessions for production and breeding. Fifty wild accessions and one Portuguese landrace were evaluated for 21 characteristics under winter Mediterranean conditions in northwestern Spain in 2001 and 2002. Accessions showed significant differences for 14 of 21 traits. Accession × environment interaction was significant for seed width and plant height. Based on multivariate analyses, 90% of the accessions grouped together indicating that genetic variation for most studied characters is limited in this germplasm. In general, accessions were late in flowering and maturity, with high levels of vegetative development, small and impermeable seeds, and dehiscent pods. However three accessions (LUP‐0077, LUP‐0080, and LUP‐0125) with high seed yield, water permeability, and relatively large pods and seeds may have potential for seed production and improvement of agronomic characteristics. In addition, LUP‐0196 produced high green mass and could be used for forage production in high rainfall cool‐temperate environments with long growing season conditions.
Leaf Trait Coloration in White Clover and Molecular Mapping of the Red Midrib and Leaflet Number Traits
Authors: Tashiro Rebecca M. , Han Yuanhong , Monteros María J. , Bouton Joseph H. , Parrott Wayne A.
Published: June 2010

White clover (Trifolium repens L.) is a highly outcrossing heterozygous allotetraploid species, for which classic inheritance studies have been inconclusive. With the aid of molecular markers, it is now possible to study the genes controlling morphological traits. The objectives of this study were to catalog the leaf marks in white clover and map the location of leaf morphological traits based on cosegregation with molecular markers. A mapping population segregating for eight morphological traits consisting of leaf marks and number of leaflets was developed and phenotyped at two different locations during the summer and winter seasons. A confirmation population, derived by selfing one of the mapping population parents, was produced and phenotyped in one location at two different times of the year. Through the use of previously published simple sequence repeat (SSR) marker maps, linkages between the mapped molecular markers and genes for three different morphological traits was identified. The red midrib and red fleck traits were found to be controlled by two closely linked dominant genes on linkage group (LG) B1. The trifoliolate trait is controlled by at least one gene on LG H1. The identification of molecular markers linked to loci affecting leaf morphology traits resolves conflicting hypotheses on the genetics of these complex traits and has potential for molecular breeding improvement of white clover.
Simple Sequence Repeat Allelic Diversity in Virginia‐Type Peanut Cultivars Released from 1943 to 2006
Authors: Milla‐Lewis Susana R. , Zuleta M. Carolina , Isleib Thomas G.
Published: June 2010

Studies on genetic diversity in Arachis spp. using microsatellite markers have included few or no commercial cultivars among the genotypes analyzed. The primary objective of this investigation was to evaluate the utility of simple sequence repeat (SSR) markers for detecting molecular polymorphism among elite virginia‐type peanut germplasm. Within that context, we had a secondary objective of assessing the impact of decades of plant breeding on allelic diversity levels among virginia‐type peanut cultivars. All U.S. virginia‐type cultivated varieties (except four) released between 1943 and 2006 were genotyped at 39 microsatellite loci. A total of 171 alleles were amplified. Allelic frequencies ranged from 0.02 to 0.97, with an average of 0.27. Although no significant difference was observed for the number of alleles present between the initial and the most recent time periods, our results indicate that levels of diversity present in virginia‐type peanuts have fluctuated significantly since the 1940s and peaked during the 1970s. Our study demonstrates that microsatellite markers may be useful for detecting molecular variation among peanut cultivars. Moreover, this is the first report of using microsatellite markers to describe genetic diversity in a collection of cultivated varieties of peanut.
Identification of Chromosome Locations of Genes Affecting Preharvest Sprouting and Seed Dormancy Using Chromosome Substitution Lines in Tetraploid Wheat (Triticum turgidum L.)
Authors: Chao Shiaoman , Xu Steven S. , Elias Elias M. , Faris Justin D. , Sorrells Mark E.
Published: June 2010

Seed dormancy, the main factor contributing to preharvest sprouting (PHS) resistance, is a complex trait and is strongly influenced by environmental growth conditions. In this study, three sets of single chromosome substitution lines, including 36 genotypes, in a durum wheat [Triticum turgidum L. ssp. durum (Desf.) Husn.] background with donor chromosomes originating from three wild emmer [T. turgidum L. ssp. dicoccoides (Körn. ex Asch. and Graebn.) Thell.] accessions were grown in nine field environments and evaluated for seed dormancy and PHS resistance. The substitution lines involving chromosome 3A were among the most dormant genotypes. Germination tests indicated that five chromosomes contained genes influencing seed dormancy at a level comparable to 3A. Results from PHS tests showed that PHS was affected by at least eight T. dicoccoides chromosomes including 3A. The chromosomes harboring genes for seed dormancy did not fully correspond with those for PHS resistance. The weak correlations between PHS and dormancy observed in this study indicate that different genes are affecting these traits and they may be differentially influenced by the environment. Nonetheless, our results revealed that genes present on five chromosomes, 2A, 2B, 3A, 4A, and 7B, were found to affect both PHS resistance and seed dormancy. These genotypes thus provide useful resources for further studies on genetic interactions that contribute to the overall phenotypic variation and on genetic dissection of quantitative trait loci underlying PHS resistance.
Transgenic Male Sterility Permits Efficient Recurrent Selection in Autogamous Crops
Authors: Tanaka Junichi
Published: June 2010

In recent decades, yield improvements of major autogamous crops have slowed. Contrastingly, the yield of maize (Zea mays L.) has continuously increased through breeding based on wide genetic diversity and recurrent selection. Recurrent selection is very powerful and is a suitable breeding system for outcrossing (allogamous) crops. To achieve recurrent selection of autogamous crops, some progress has been made in rice (Oryza sativa L.), sorghum [Sorghum bicolor (L.) Moench], and soybean [Glycine max (L.) Merr.] using genetic male sterility. However, this approach has not provided major improvements for the breeding of autogamous crops, because it is laborious or based on specific properties of the crops. To prevent this from becoming a bottleneck for the use of recurrent selection in autogamous crops, the author devised an efficient recurrent selection system based on transgenic male sterility, herbicide tolerance, and conditional lethality suitable for use with autogamous crops. This system offers three advantages. First, it can be applied on a large scale while permitting continuous recurrent selection. Second, the cultivars that are the final products of this breeding do not contain the transgenes introduced by this system. Third, the transgenic plants cannot produce pollen and therefore cannot cross naturally with cultivated crops or related wild species. This paper proposes an efficient recurrent selection for autogamous crops using transgenic male sterility.
3D Digital Imaging Correlation: Applications to Tire Testing
Authors: Moser Russ A. , Sube H. James , Turner John L. , Zakelj Paul
Published: June 2010

Three-dimensional digital imaging correlation (DIC) techniques are a viable method for measuring surface displacements and strains on tires. DIC provides the capability to measure the full-field noncontact tire surface deformation and strain state, which supports multiple objectives: validation of tire models based on finite element (FE) predictions, setting targets for improving FE predictions and providing insight into the tire deformation state under static and dynamic conditions. A method for verifying the accuracy of the DIC measurement process is presented whereby a thin, rectangular test sample of rubber material is subjected to a combination of strains and rigid body motions of known amounts. Once the measurement technique is proven accurate with a simple specimen, the focus shifts to the objectives explained above. Tire surface strains will be discussed for purposes of validating model predictions of sidewall and belt edge strains. Several types of specimen geometries will be reviewed and their effect on material properties will be presented. Also, the DIC technique can provide insight into complex physical problems that may otherwise be very difficult to measure. Some examples presented here include tire sidewall standing waves at high speeds and strains near tread lugs of agricultural tires. The DIC measurement method is an accurate, noncontacting full field technique for measuring in-plane surface displacements and strains of the magnitudes encountered in tire analysis. This technique serves many functions and has become a valuable tool for both tire testing and development.
Aspiration Technique Improves Reliability of Endoscopically Directed Middle Meatal Cultures in Pediatric Rhinosinusitis
Authors: Hsin Chung-Han , Chen Tsai-Hsin , Su Mao-Chang , Jiang Rong-San , Liu Chia-Ming
Published: June 2010

Background

Most studies demonstrated that the results of endoscopically directed middle meatal cultures (EDMMC) compare favorable with those of maxillary sinus taps in adults rhinosinusitis. Studies comparing results of EDMMC and antral puncture cultures in pediatric rhinosinusitis, however, revealed a decreased correlation. Sampling by suction aspiration was considered likely to improve the reliability of culture.

Objective

The aim of this study was to compare the microbiology results obtained by EDMMC using swabs or suction aspiration with the results of maxillary sinus taps in pediatric rhinosinusitis.

Methods

Thirty-one children with chronic rhinosinusitis were enrolled. Patients enrolled in 2007 (group A), underwent EDMMC using a swab, whereas those enrolled in 2008 (group B) underwent EDMMC using suction aspiration. Results obtained by EDMMC were compared with those of maxillary sinus taps.

Results

In group A, 29 paired cultures were obtained from 15 patients. In group B, 30 paired cultures were obtained from 16 patients. In group A, EDMMC by swab demonstrated a sensitivity of 52%, a specificity of 100%, and a correlation of 66%. In group B, EDMMC by suction aspiration provided a sensitivity of 86%, a specificity of 100%, and a correlation of 87%. The difference in density of growth between EDMMC with swab and maxillary sinus tap was not significant, but the difference between EDMMC with aspiration and maxillary sinus tap was significant.

Conclusion

Aspiration technique can significantly enhance the reliability of endoscopy cultures in children with rhinosinusitis, probably by increasing the amount of specimen obtained.