bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Cross-Reactive Epitopes on the Conserved 47-Kilodalton Antigen ofOrientia tsutsugamushiand Human Serine Protease
Authors: Chen Hua-Wei , Zhang Zhiwen , Huber Erin , Chao Chien-Chung , Wang Hui , Dasch Gregory A. , Ching Wei-Mei 
Published: March 2009

ABSTRACTOrientia tsutsugamushiis the causative agent of scrub typhus. One of the protein antigens of this species, the conserved 47-kDa protein (HtrA), has been shown to induce an antibody response in patients and can provide protective immunity against live challenge byOrientiain mice. Pepscan experiments identified many peptide epitope clusters in different parts of this protein. The majority of the most reactive epitopes are located at the C terminus of the protein (from amino acid 333 to amino acid 430). Protein sequence analysis revealed that the 47-kDa protein contains a trypsin domain and has sequence homology to human serine protease HtrA1 (hHtrA1). As the 47-kDa protein is a potential vaccine candidate and its ability to induce autoimmunity is a concern, the reactivity of scrub typhus patient sera with purified recombinant 47-kDa and hHtrA1 proteins was tested. A significant percentage (>20%) of scrub typhus patient sera reacted strongly with recombinant hHTRA1 and two of the antigenic polypeptide epitopes in hHtrA1. These findings suggest that the safety of the full-length 47-kDa antigen as a vaccine candidate is a significant issue due to its cross-reactivity with a human protein, which may also contribute to autoimmune responses or enhanced pathology in some scrub typhus patients.
Can loud noise cause acoustic neuroma? Analysis of the INTERPHONE study in France
Authors: Hours M , Bernard M , Arslan M , Montestrucq L , Richardson L , Deltour I , Cardis E 
Published: March 2009

Objectives:To investigate possible associations between risk of acoustic neuroma and exposure to loud noise in leisure and occupational settings.Methods:A case-control study was conducted in France within the international INTERPHONE study. The cases were the 108 subjects diagnosed with acoustic neuroma between 1 June 2000 and 31 August 2003. Two controls per case were selected from the electoral rolls and individually matched for gender, age (5 years) and area (local authority district) of residence at the time of the case diagnosis. Multivariate analyses were conducted using conditional logistic regression. Adjustment was made for socioeconomic status.Results:Acoustic neuroma was found to be associated with loud noise exposure (odds ratio (OR) = 2.55; 95% CI 1.35 to 4.82), both in leisure settings, particularly when listening to loud music (OR = 3.88; 95% CI 1.48 to 10.17) and at work (OR = 2.26; 95% CI 1.08 to 4.72). This risk increased with exposure duration (>6 years’ leisure exposure: OR = 3.15; 95% CI 1.07 to 9.24). Risk varied according to the type of noise (continuous or explosive vs intermittent).Conclusion:The present results agree with other recent reports implicating loud noise in the risk of acoustic neuroma.
Improved cure of bacterial vaginosis with single dose of tinidazole (2 g),Lactobacillus rhamnosusGR-1, andLactobacillus reuteriRC-14: a randomized, double-blind, placebo-controlled trial
Authors: Martinez Rafael C. R. , Franceschini Sílvio A. , Patta Maristela C. , Quintana Silvana M. , Gomes Bruna C. , De Martinis Elaine C. P. , Reid Gregor 
Published: March 2009

Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by depletion of the indigenous lactobacilli. Antimicrobial therapy is often ineffective. We hypothesized that probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 might provide an adjunct to antimicrobial treatment and improve cure rates. Sixty-four Brazilian women diagnosed with BV were randomly assigned to receive a single dose of tinidazole (2 g) supplemented with either 2 placebo capsules or 2 capsules containing L. rhamnosus GR-1 and L. reuteri RC-14 every morning for the following 4 weeks. At the end of treatment (day 28), the probiotic group had a significantly higher cure rate of BV (87.5%) than the placebo group (50.0%) (p = 0.001). In addition, according to the Gram-stain Nugent score, more women were assessed with “normal” vaginal microbiota in the probiotic group (75.0% vs. 34.4% in the placebo group; p = 0.011). This study shows that probiotic lactobacilli can provide benefits to women being treated with antibiotics for an infectious condition.
Ecological correlates of trophic polyphenism in spadefoot tadpoles inhabiting playas
Authors: Ghioca-Robrecht D. M. , Smith L. M. , Densmore L. D. 
Published: March 2009

Polyphenism in larval amphibians has been related to several factors, including wetland hydroperiod, food availability, competition, and predation. Spadefoot toads (genus Spea Cope, 1866) often exhibit a trophic polyphenism by developing distinct carnivore and omnivore larval morphotypes. Using a multimodel selection approach, we investigated the influence of land use (cropland vs. grassland type) and differences in annual precipitation on morphotype expression in Plains spadefoot ( Spea bombifrons (Cope, 1863)) and New Mexico spadefoot ( Spea multiplicata (Cope, 1863)) toads in playas. We also examined the relative importance of tadpole density, tadpole age, water-loss stress, wetland size, density of larval mole salamanders (genus Ambystoma Tschudi, 1838; a predator on Spea tadpoles), and food resources on morph occurrence. The carnivore morphotype developed almost exclusively in S. bombifrons and rarely in S. multiplicata regardless of land use. Habitat availability measured by water-loss rate, as well as predation risk and tadpole age, were the most important factors influencing carnivore proportions. Ambystoma density was positively associated, whereas water-depth loss and tadpole age were negatively associated with the proportion of carnivores. The greatest proportion of carnivores was observed in grassland playas, which had the highest density of Ambystoma predators, longest hydroperiods, and experienced water-depth gain. Fairy shrimp density was not correlated with the proportion of carnivores. Upland land use through cultivation-associated erosion is altering wetland trophic structure, which further influences morphotype expression in Spea tadpoles and playa amphibian community structure.
WORLD-CLASS OR GOOD ENOUGH — THE CHOICE OF PARTNER WHEN OUTSOURCING NEW PRODUCT DEVELOPMENT IN MEDIUM-SIZED FIRMS
Authors: RUNDQUIST JONAS 
Published: March 2009

Research on outsourcing normally focuses on outsourcing of production and often uses large firms as samples. Only a few studies address the outsourcing of services or knowledge-intensive activities such as new product development (NPD), and especially in the context of medium-sized firms. Our earlier research in medium-sized firms indicates that outsourcing of NPD is frequent in medium-sized firms, and that there is a lack of knowledge about the phenomenon. This article offers a theoretical framework to study the outsourcing of NPD, and includes the results from a longitudinal case study carried out in six Swedish medium-sized firms to help understand the rationales behind outsourcing of NPD. Results from the present study indicate that 'good enough' is the keyword for medium-sized firms with limited resources. This means that it is considered more important with proximity and trust than world class competence, since close and frequent contacts are crucial, when outsourcing knowledge-intensive activities such as NPD. A conceptual model and a definition of the good enough concept are also presented.
THE BURNSIDE RING-VALUED MORSE FORMULA FOR VECTOR FIELDS ON MANIFOLDS WITH BOUNDARY
Authors: KATZ GABRIEL 
Published: March 2009

Let G be a compact Lie group and A(G) its Burnside Ring. For a compact smooth n-dimensional G-manifold X equipped with a generic G-invariant vector field v, we prove an equivariant analog of the Morse formula [Formula: see text] which takes its values in A(G). Here Ind G(v) denotes the equivariant index of the field v, [Formula: see text] the v-induced Morse stratification (see [10]) of the boundary ∂X, and [Formula: see text] the class of the (n - k)-manifold [Formula: see text] in A(G). We examine some applications of this formula to the equivariant real algebraic fields v in compact domains X ⊂ ℝn defined via a generic polynomial inequality. Next, we link the above formula with the equivariant degrees of certain Gauss maps. This link is an equivariant generalization of Gottlieb's formulas ([3, 4]).
Effect of bosentan upon pulmonary hypertension in chronic obstructive pulmonary disease
Authors: Valerio Giuseppe , Bracciale Pierluigi , Grazia D'Agostino Anna 
Published: March 2009

Background: Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is mainly determined by hypoxemia under respiratory failure by means of the functional hypoxemic vasoconstrictor response. Organic changes of vessels, pulmonary vascular remodelling, is gaining increasing relevance. An imbalance of endothelial products takes place with overload of vasoconstrictors and thrombogenic autacoids over vasodilators and anticoagulant factors. Among vasoconstrictors, endothelin is claimed to be an important factor. Our aim is to assess the effect of the anti-endothelin drug Bosentan on pulmonary hemodynamics and lung function in patients affected by COPD and PH. Methods: Bosentan was administered to 16 patients for a period of 18 months, while another 16 patients with overlapping features was used as a control group. Pulmonary function test, hemodynamics, effort performance, dyspnoea ratings and quality of life were recorded at the beginning and after 18 months under stable state. Results: Bosentan treatment resulted in a significant improvement of PH from 37 + 5 to 31 + 6mm Hg and pulmonary vascular resistance from 442 + 192 to 392 + 180dynes cm2 and 6MWD from 256 + 118 to 321 + 122m and BODE index from 6.6 + 2.8 to 5.5 + 3U. The effect was most striking in the 30% of patients in GOLD stage III and IV. Most patients in stage IV did not improve, but in all patients the treatment stopped the progressive worsening of hemodynamics over time. The study also highlights the need to identify patients with high pulmonary arterial pressure contrasting with moderate respiratory disease stages, in whom the predominant problem is evidently vascular disease. Conclusion: This preliminary report suggests that the use of Bosentan in the treatment of PH in COPD is beneficial.
Therapeutic targeting of MLL
Authors: Liedtke Michaela , Cleary Michael L. 
Published: March 2009

AbstractTreatment of hematologic malignancies is evolving from a uniform approach to targeted therapies directed at the underlying molecular abnormalities of disease. The mixed lineage leukemia (MLL) proto-oncogene is a recurrent site of genetic rearrangements in acute leukemias; and since its discovery in 1992, many advances have been made in understanding its role in leukemogenesis. A variety of MLL translocation partners have been described, and detailed structure/function studies have identified functional domains that are required for transformation. Proteins associated with the MLL core complex or its fusion partners have been isolated and characterized for their critical roles in leukemia pathogenesis. Downstream mediators of MLL transcriptional regulation and multiple collaborating signaling pathways have been described and characterized. These advances in our understanding of MLL-related leukemogenesis provide a foundation for ongoing and future efforts to develop novel therapeutic strategies that will hopefully result in better treatment outcomes.
Activation of an AMP-activated protein kinase is involved in post-diapause development of Artemia franciscana encysted embryos
Authors: Zhu Xiao-Jing , Dai Jie-Qiong , Tan Xin , Zhao Yang , Yang Wei-Jun 
Published: March 2009

Abstract

Background
Cysts of Artemia can remain in a dormant state for long periods with a very low metabolic rate, and only resume their development with the approach of favorable conditions. The post-diapause development is a very complicated process involving a variety of metabolic and biochemical events. However, the intrinsic mechanisms that regulate this process are unclear.

Results
Herein we report the specific activation of an AMP-activated protein kinase (AMPK) in the post-diapause developmental process of Artemia. Using a phospho-AMPKα antibody, AMPK was shown to be phosphorylated in the post-diapause developmental process. Results of kinase assay analysis showed that this phosphorylation is essential for AMPK activation. Using whole-mount immunohistochemistry, phosphorylated AMPK was shown to be predominantly located in the ectoderm of the early developed embryos in a ring shape; however, the location and shape of the activation region changed as development proceeded. Additionally, Western blotting analysis on different portions of the cyst extracts showed that phosphorylated AMPKα localized to the nuclei and this location was not affected by intracellular pH. Confocal microscopy analysis of immunofluorescent stained cyst nuclei further showed that AMPKα localized to the nuclei when activated. Moreover, cellular AMP, ADP, and ATP levels in developing cysts were determined by HPLC, and the results showed that the activation of Artemia AMPK may not be associated with cellular AMP:ATP ratios, suggesting other pathways for regulation of Artemia AMPK activity.

Conclusion
Together, we report evidence demonstrating the activation of AMPK in Artemia developing cysts and present an argument for its role in the development-related gene expression and energy control in certain cells during post-diapause development of Artemia.
Transcriptomic basis for an antiserum against Micrurus corallinus (coral snake) venom
Authors: Leão Luciana I , Ho Paulo L , Junqueira-de-Azevedo Inacio de LM 
Published: March 2009

Abstract

Background

Micrurus corallinus (coral snake) is a tropical forest snake belonging to the family Elapidae. Its venom shows a high neurotoxicity associated with pre- and post-synaptic toxins, causing diaphragm paralysis, which may result in death. In spite of a relatively small incidence of accidents, serum therapy is crucial for those bitten. However, the adequate production of antiserum is hampered by the difficulty in obtaining sufficient amounts of venom from a small snake with demanding breeding conditions. In order to elucidate the molecular basis of this venom and to uncover possible immunogens for an antiserum, we generated expressed sequences tags (ESTs) from its venom glands and analyzed the transcriptomic profile. In addition, their immunogenicity was tested using DNA immunization.

Results
A total of 1438 ESTs were generated and grouped into 611 clusters. Toxin transcripts represented 46% of the total ESTs. The two main toxin classes consisted of three-finger toxins (3FTx) (24%) and phospholipases A2 (PLA2s) (15%). However, 8 other classes of toxins were present, including C-type lectins, natriuretic peptide precursors and even high-molecular mass components such as metalloproteases and L-amino acid oxidases. Each class included an assortment of isoforms, some showing evidence of alternative splicing and domain deletions. Five antigenic candidates were selected (four 3FTx and one PLA2) and used for a preliminary study of DNA immunization. The immunological response showed that the sera from the immunized animals were able to recognize the recombinant antigens.

Conclusion
Besides an improvement in our knowledge of the composition of coral snake venoms, which are very poorly known when compared to Old World elapids, the expression profile suggests abundant and diversified components that may be used in future antiserum formulation. As recombinant production of venom antigens frequently fails due to complex disulfide arrangements, DNA immunization may be a viable alternative. In fact, the selected candidates provided an initial evidence of the feasibility of this approach, which is less costly and not dependent on the availability of the venom.
The mitochondrial genomes of Ancylostoma caninum and Bunostomum phlebotomum – two hookworms of animal health and zoonotic importance
Authors: Jex Aaron R , Waeschenbach Andrea , Hu Min , van Wyk Jan A , Beveridge Ian , Littlewood D Timothy J , Gasser Robin B 
Published: March 2009

Abstract

Background
Hookworms are blood-feeding nematodes that parasitize the small intestines of many mammals, including humans and cattle. These nematodes are of major socioeconomic importance and cause disease, mainly as a consequence of anaemia (particularly in children or young animals), resulting in impaired development and sometimes deaths. Studying genetic variability within and among hookworm populations is central to addressing epidemiological and ecological questions, thus assisting in the control of hookworm disease. Mitochondrial (mt) genes are known to provide useful population markers for hookworms, but mt genome sequence data are scant.

Results
The present study characterizes the complete mt genomes of two species of hookworm, Ancylostoma caninum (from dogs) and Bunostomum phlebotomum (from cattle), each sequenced (by 454 technology or primer-walking), following long-PCR amplification from genomic DNA (~20–40 ng) isolated from individual adult worms. These mt genomes were 13717 bp and 13790 bp in size, respectively, and each contained 12 protein coding, 22 transfer RNA and 2 ribosomal RNA genes, typical for other secernentean nematodes. In addition, phylogenetic analysis (by Bayesian inference and maximum likelihood) of concatenated mt protein sequence data sets for 12 nematodes (including Ancylostoma caninum and Bunostomum phlebotomum), representing the Ascaridida, Spirurida and Strongylida, was conducted. The analysis yielded maximum statistical support for the formation of monophyletic clades for each recognized nematode order assessed, except for the Rhabditida.

Conclusion
The mt genomes characterized herein represent a rich source of population genetic markers for epidemiological and ecological studies. The strong statistical support for the construction of phylogenetic clades and consistency between the two different tree-building methods employed indicate the value of using whole mt genome data sets for systematic studies of nematodes. The grouping of the Spirurida and Ascaridida to the exclusion of the Strongylida was not supported in the present analysis, a finding which conflicts with the current evolutionary hypothesis for the Nematoda based on nuclear ribosomal gene data.
Discovery and identification of potential biomarkers of pediatric Acute Lymphoblastic Leukemia
Authors: Shi Linan , Zhang Jun , Wu Peng , Feng Kai , Li Jing , Xie Zhensheng , Xue Peng , Cai Tanxi , Cui Ziyou , Chen Xiulan , Hou Junjie , Zhang Jianzhong , Yang Fuquan 
Published: March 2009

Abstract

Background
Acute lymphoblastic leukemia (ALL) is a common form of cancer in children. Currently, bone marrow biopsy is used for diagnosis. Noninvasive biomarkers for the early diagnosis of pediatric ALL are urgently needed. The aim of this study was to discover potential protein biomarkers for pediatric ALL.

Methods
Ninety-four pediatric ALL patients and 84 controls were randomly divided into a "training" set (45 ALL patients, 34 healthy controls) and a test set (49 ALL patients, 30 healthy controls and 30 pediatric acute myeloid leukemia (AML) patients). Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS). A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays.

Results
A total of 7 protein peaks (9290 m/z, 7769 m/z, 15110 m/z, 7564 m/z, 4469 m/z, 8937 m/z, 8137 m/z) were found with differential expression levels in the sera of pediatric ALL patients and controls using SELDI-TOF-MS and then analyzed by BPS to construct a classification model in the "training" set. The sensitivity and specificity of the model were found to be 91.8%, and 90.0%, respectively, in the test set. Two candidate protein peaks (7769 and 9290 m/z) were found to be down-regulated in ALL patients, where these were identified as platelet factor 4 (PF4) and pro-platelet basic protein precursor (PBP). Two other candidate protein peaks (8137 and 8937 m/z) were found up-regulated in the sera of ALL patients, and these were identified as fragments of the complement component 3a (C3a).

Conclusion
Platelet factor (PF4), connective tissue activating peptide III (CTAP-III) and two fragments of C3a may be potential protein biomarkers of pediatric ALL and used to distinguish pediatric ALL patients from healthy controls and pediatric AML patients. Further studies with additional populations or using pre-diagnostic sera are needed to confirm the importance of these findings as diagnostic markers of pediatric ALL.
Construction and validation of a short-form Quality-Of-Life Scale for Chinese Patients with Benign Prostatic Hyperplasia
Authors: Guo Yanfang , Shi Jingcheng , Hu Ming , Sun Zhenqiu 
Published: March 2009

Abstract

Background
In 2003, a 74-item quality-of-life (QOL) scale for Chinese benign prostatic hyperplasia (BPH) patients (BPH-QLS) was developed. Although the scale displayed good reliability and validity, the time required to complete it may limit its use. The purpose of this study was to construct and validate a short-form quality-of-life (QOL) scale for Chinese patients with Benign Prostatic Hyperplasia (BPH).

Methods
According to the previously published 74-item quality of life scale for BPH (BPH-QLS), we developed a pool of items, then condensed these items and validated the shortened scale, based on collected data from 163 patients with BPH. We used eight methods to reduce the items.

Results
A 33-item QOL scale for BPH (short-form of BPH-QLS) was constructed. The time take by the new scale was much shorter than the original one. There was no significant difference between the 33-item scale and 74-item scale, in terms of reliability. Moreover, the 33-item BPH-QLS showed a high correlation with the 74-item BPH-QLS (r = 0.971). Scores generated by the two scales were not only parallel and coincident but also at the same level.

Conclusion
We concluded that the reliability and validity of the short form of BPH-QLS is close to those of the 74-item BPH-QLS. It should be a good choice in clinical practice for its greater compliance and clinical feasibility.