bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Hepatic Receptors Cooperate to Eliminate Secretory Mucins Aberrantly Entering the Bloodstream: Are Circulating Cancer Mucins the “Tip of the Iceberg”?
Authors: Wahrenbrock Mark G. , Varki Ajit 
Published: February 2006

Abstract
Hollow organs lined by columnar epithelial cells normally secrete mucins and their proteolytic fragments vectorially into the lumen. These heterogeneously O-glycosylated molecules are known to aberrantly enter the bloodstream in the setting of epithelial carcinomas and possibly during injury or inflammation. We have recently shown that carcinoma mucin fragments can trigger the rapid formation of platelet-rich microthrombi in vivo. Thus, mechanisms to clear such aberrantly secreted mucins must exist. Indeed, we found that i.v. injected carcinoma mucin fragments had an ∼1 minute half-life in mice, which was primarily due to rapid clearance by hepatic reticuloendothelial cells. Inhibition of known glycan-recognizing hepatic clearance receptors showed involvement of multiple partially overlapping clearance systems. Studies of genetically deficient mice and incomplete competition between different mucins confirmed this result. Thus, multiple hepatic clearance receptors cooperate to eliminate secretory mucins entering the circulation, limiting potential pathology. This may also explain why mucin-type clustered O-glycosylation is rare on plasma proteins. Notably, small subsets of injected carcinoma mucins remained unrecognized by clearance systems, had a much longer half-life, and carried highly sialylated O-glycans. Similar circulating mucins were found in tumor-bearing mice despite lack of saturation of hepatic clearance mechanisms. Thus, circulating cancer mucins currently used as clinical diagnostic markers likely represent only the clearance-resistant “tip of the iceberg.” Such aberrantly circulating mucins could play pathologic roles not only in cancer but also during injury or inflammation of hollow organs and in liver disease. (Cancer Res 2006; 66(4): 2433-41)
Combining predictions in a simplified 4-Θ methodology for creep life assessment: An application to 2Cr—1Mo steel
Authors: Evans M. 
Published: February 2006

A simplification of the 4-Θ methodology is proposed and then used to predict creep properties under non-accelerated test conditions using data on 2Cr–1Mo steel. In the proposed simplification, creep rates at very low strains were first used to predict the minimum creep rates which are then used in the Monkman–Grant relation to predict times to failure. Because various strains can be used in this simplification, predictions using creep rates at various strains were combined in an optimal manner. These predictions were then compared with those obtained through the traditional application of the 4-Θ methodology. These predictions were assessed using the mean absolute percentage error (MAPE) and mean square error (MSE) which were further decomposed into systematic and random components. When considering the accuracy of the extrapolations for both minimum creep rates and times to failure, most of the simplified 4-Θ models produced lower MSE and MAPE compared with the traditional implementation of the 4-Θ methodology. All models also had very similar random components of the MSE. A simplified 4-Θ model that used creep rates measured at higher strain usually produced better extrapolations (as measured by the MAPE) than those obtained by combing the extrapolations from a number of simplified 4-Θ models. However, combing predictions in this way tended to increase the random component of the MSE.
Coordination of erythropoiesis by the transcription factor c-Myb
Authors: Vegiopoulos Alexandros , García Paloma , Emambokus Nikla , Frampton Jon 
Published: February 2006

Abstract
The involvement of the transcription factor c-Myb in promoting the proliferation and inhibition of erythroid cell differentiation has been established in leukemia cell models. The anemia phenotype observed in c-myb knockout and knockdown mice highlights a critical role for c-Myb in erythropoiesis. However, determining the reason for the failure of erythropoiesis in these mice and the precise function of c-Myb in erythroid progenitors remains elusive. We examined erythroid development under conditions of reduced c-Myb protein levels and report an unexpected role for c-Myb in the promotion of commitment to the erythroid lineage and progression to erythroblast stages. c-myb knockdown erythroid colony-forming unit (CFU-E) stage progenitors displayed an immature phenotype and aberrant expression of several hematopoietic regulators. To extend our findings, we analyzed the response of normal enriched erythroid progenitors to inducible disruption of a floxed c-myb allele. In agreement with the c-myb knockdown phenotype, we show that c-Myb is strictly required for expression of the c-Kit receptor in erythroid cells.
Role of transforming growth factor-β in hematologic malignancies
Authors: Dong Mei , Blobe Gerard C. 
Published: February 2006

AbstractThe transforming growth factor-β (TGF-β) signaling pathway is an essential regulator of cellular processes, including proliferation, differentiation, migration, and cell survival. During hematopoiesis, the TGF-β signaling pathway is a potent negative regulator of proliferation while stimulating differentiation and apoptosis when appropriate. In hematologic malignancies, including leukemias, myeloproliferative disorders, lymphomas, and multiple myeloma, resistance to these homeostatic effects of TGF-β develops. Mechanisms for this resistance include mutation or deletion of members of the TGF-β signaling pathway and disruption of the pathway by oncoproteins. These alterations define a tumor suppressor role for the TGF-β pathway in human hematologic malignancies. On the other hand, elevated levels of TGF-β can promote myelofibrosis and the pathogenesis of some hematologic malignancies through their effects on the stroma and immune system. Advances in the TGF-β signaling field should enable targeting of the TGF-β signaling pathway for the treatment of hematologic malignancies.
Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling
Authors: Jang An-Soo , Choi Inseon-S , Lee Jae-Hyuk , Park Chang-Soo , Park Choon-Sik 
Published: February 2006

Abstract

Background
Short-term exposure to high concentrations of ozone has been shown to increase airway hyper-responsiveness (AHR). Because the changes in AHR and airway inflammation and structure after chronic ozone exposure need to be determined, the goal of this study was to investigate these effects in a murine model of allergic airway disease.

Methods
We exposed BALB/c mice to 2 ppm ozone for 4, 8, and 12 weeks. We measured the enhanced pause (Penh) to methacholine and performed cell differentials in bronchoalveolar lavage fluid. We quantified the levels of IL-4 and IFN-γ in the supernatants of the bronchoalveolar lavage fluids using enzyme immunoassays, and examined the airway architecture under light and electron microscopy.

Results
The groups exposed to ozone for 4, 8, and 12 weeks demonstrated decreased Penh at methacholine concentrations of 12.5, 25, and 50 mg/ml, with a dose-response curve to the right of that for the filtered-air group. Neutrophils and eosinophils increased in the group exposed to ozone for 4 weeks compared to those in the filtered-air group. The ratio of IL-4 to INF-γ increased significantly after exposure to ozone for 8 and 12 weeks compared to the ratio for the filtered-air group. The numbers of goblet cells, myofibroblasts, and smooth muscle cells showed time-dependent increases in lung tissue sections from the groups exposed to ozone for 4, 8, and 12 weeks.

Conclusion
These findings demonstrate that the increase in AHR associated with the allergic airway does not persist during chronic ozone exposure, indicating that airway remodeling and adaptation following repeated exposure to air pollutants can provide protection against AHR.
Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation: associations with asthmatic phenotype, airway inflammation and β2-agonist use
Authors: Hastie Annette T , Wu Min , Foster Gayle C , Hawkins Gregory A , Batra Vikas , Rybinski Katherine A , Cirelli Rosemary , Zangrilli James G , Peters Stephen P 
Published: February 2006

Abstract

Background
Vasodilator-stimulated phosphoprotein (VASP) mediates focal adhesion, actin filament binding and polymerization in a variety of cells, thereby inhibiting cell movement. Phosphorylation of VASP via cAMP and cGMP dependent protein kinases releases this "brake" on cell motility. Thus, phosphorylation of VASP may be necessary for epithelial cell repair of damage from allergen-induced inflammation. Two hypotheses were examined: (1) injury from segmental allergen challenge increases VASP phosphorylation in airway epithelium in asthmatic but not nonasthmatic normal subjects, (2) regular in vivo β2-agonist use increases VASP phosphorylation in asthmatic epithelium, altering cell adhesion.

Methods
Bronchial epithelium was obtained from asthmatic and non-asthmatic normal subjects before and after segmental allergen challenge, and after regularly inhaled albuterol, in three separate protocols. VASP phosphorylation was examined in Western blots of epithelial samples. DNA was obtained for β2-adrenergic receptor haplotype determination.

Results
Although VASP phosphorylation increased, it was not significantly greater after allergen challenge in asthmatics or normals. However, VASP phosphorylation in epithelium of nonasthmatic normal subjects was double that observed in asthmatic subjects, both at baseline and after challenge. Regularly inhaled albuterol significantly increased VASP phosphorylation in asthmatic subjects in both unchallenged and antigen challenged lung segment epithelium. There was also a significant increase in epithelial cells in the bronchoalveolar lavage of the unchallenged lung segment after regular inhalation of albuterol but not of placebo. The haplotypes of the β2-adrenergic receptor did not appear to associate with increased or decreased phosphorylation of VASP.

Conclusion
Decreased VASP phosphorylation was observed in epithelial cells of asthmatics compared to nonasthmatic normals, despite response to β-agonist. The decreased phosphorylation does not appear to be associated with a particular β2-adrenergic receptor haplotype. The observed decrease in VASP phosphorylation suggests greater inhibition of actin reorganization which is necessary for altering attachment and migration required during epithelial repair.
Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity
Authors: Kang Jungseog , Gocke Christian B , Yu Hongtao 
Published: February 2006

Abstract

Background
Sumoylation has emerged as an important posttranslational regulatory mechanism for transcription factors and cofactors. Sumoylation of many transcription factors represses their transcriptional activities. The myocyte enhancer factor 2 (MEF2) family of transcription factors plays an important role in regulating gene expression during myogenesis and has been recently shown to be sumoylated.

Results
Consistent with earlier reports, we show that sumoylation of MEF2C at K391 inhibits its transcriptional activity. Sumoylation of MEF2C does not block its DNA-binding activity. A small C-terminal fragment of MEF2C containing K391, referred to as delta-N2-MEF2C, is efficiently sumoylated and, when targeted to DNA, represses transcription at neighbouring promoters. Because delta-N2-MEF2C lacks the binding site for class II histone deacetylases (HDACs), this result suggests that sumoylation of MEF2C may help to recruit transcriptional repressors other than these HDACs. Intriguingly, we show that phosphorylation of S396 in MEF2C, a residue in close proximity to the major sumoylation site (K391) and known to be phosphorylated in vivo, enhances sumoylation of delta- N2-MEF2C in vitro. The S396A mutation reduces sumoylation of MEF2C in vivo and enhances the transcription activity of MEF2C in reporter assays.

Conclusion
We propose that phosphorylation of MEF2C at S396 facilitates its sumoylation at K391, which in turn recruits yet unidentified co-repressors to inhibit transcription. Our studies further suggest that sumoylation motifs containing a phosphorylated serine or an acidic residue at the +5 position might be more efficiently sumoylated.
Algebraic comparison of metabolic networks, phylogenetic inference, and metabolic innovation
Authors: Forst Christian V , Flamm Christoph , Hofacker Ivo L , Stadler Peter F 
Published: February 2006

Abstract

Background
Comparison of metabolic networks is typically performed based on the organisms' enzyme contents. This approach disregards functional replacements as well as orthologies that are misannotated. Direct comparison of the structure of metabolic networks can circumvent these problems.

Results
Metabolic networks are naturally represented as directed hypergraphs in such a way that metabolites are nodes and enzyme-catalyzed reactions form (hyper)edges. The familiar operations from set algebra (union, intersection, and difference) form a natural basis for both the pairwise comparison of networks and identification of distinct metabolic features of a set of algorithms. We report here on an implementation of this approach and its application to the procaryotes.

Conclusion
We demonstrate that metabolic networks contain valuable phylogenetic information by comparing phylogenies obtained from network comparisons with 16S RNA phylogenies. The algebraic approach to metabolic networks is suitable to study metabolic innovations in two sets of organisms, free living microbes and Pyrococci, as well as obligate intracellular pathogens.
BIOZON: a system for unification, management and analysis of heterogeneous biological data
Authors: Birkland Aaron , Yona Golan 
Published: February 2006

Abstract

Background
Integration of heterogeneous data types is a challenging problem, especially in biology, where the number of databases and data types increase rapidly. Amongst the problems that one has to face are integrity, consistency, redundancy, connectivity, expressiveness and updatability.

Description
Here we present a system (Biozon) that addresses these problems, and offers biologists a new knowledge resource to navigate through and explore. Biozon unifies multiple biological databases consisting of a variety of data types (such as DNA sequences, proteins, interactions and cellular pathways). It is fundamentally different from previous efforts as it uses a single extensive and tightly connected graph schema wrapped with hierarchical ontology of documents and relations. Beyond warehousing existing data, Biozon computes and stores novel derived data, such as similarity relationships and functional predictions. The integration of similarity data allows propagation of knowledge through inference and fuzzy searches. Sophisticated methods of query that span multiple data types were implemented and first-of-a-kind biological ranking systems were explored and integrated.

Conclusion
The Biozon system is an extensive knowledge resource of heterogeneous biological data. Currently, it holds more than 100 million biological documents and 6.5 billion relations between them. The database is accessible through an advanced web interface that supports complex queries, "fuzzy" searches, data materialization and more, online at http://biozon.org.
Instance-based concept learning from multiclass DNA microarray data
Authors: Berrar Daniel , Bradbury Ian , Dubitzky Werner 
Published: February 2006

Abstract

Background
Various statistical and machine learning methods have been successfully applied to the classification of DNA microarray data. Simple instance-based classifiers such as nearest neighbor (NN) approaches perform remarkably well in comparison to more complex models, and are currently experiencing a renaissance in the analysis of data sets from biology and biotechnology. While binary classification of microarray data has been extensively investigated, studies involving multiclass data are rare. The question remains open whether there exists a significant difference in performance between NN approaches and more complex multiclass methods. Comparative studies in this field commonly assess different models based on their classification accuracy only; however, this approach lacks the rigor needed to draw reliable conclusions and is inadequate for testing the null hypothesis of equal performance. Comparing novel classification models to existing approaches requires focusing on the significance of differences in performance.

Results
We investigated the performance of instance-based classifiers, including a NN classifier able to assign a degree of class membership to each sample. This model alleviates a major problem of conventional instance-based learners, namely the lack of confidence values for predictions. The model translates the distances to the nearest neighbors into 'confidence scores'; the higher the confidence score, the closer is the considered instance to a pre-defined class. We applied the models to three real gene expression data sets and compared them with state-of-the-art methods for classifying microarray data of multiple classes, assessing performance using a statistical significance test that took into account the data resampling strategy. Simple NN classifiers performed as well as, or significantly better than, their more intricate competitors.

Conclusion
Given its highly intuitive underlying principles – simplicity, ease-of-use, and robustness – the k-NN classifier complemented by a suitable distance-weighting regime constitutes an excellent alternative to more complex models for multiclass microarray data sets. Instance-based classifiers using weighted distances are not limited to microarray data sets, but are likely to perform competitively in classifications of high-dimensional biological data sets such as those generated by high-throughput mass spectrometry.
Rate of promoter class turn-over in yeast evolution
Authors: Bazykin Georgii A , Kondrashov Alexey S 
Published: February 2006

Abstract

Background
Phylogenetic conservation at the DNA level is routinely used as evidence of molecular function, under the assumption that locations and sequences of functional DNA segments remain invariant in evolution. In particular, short DNA segments participating in initiation and regulation of transcription are often conserved between related species. However, transcription of a gene can evolve, and this evolution may involve changes of even such conservative DNA segments. Genes of yeast Saccharomyces have promoters of two classes, class 1 (TATA-containing) and class 2 (non-TATA-containing).

Results
Comparison of upstream non-coding regions of orthologous genes from the five species of Saccharomyces sensu stricto group shows that among 212 genes which very likely have class 1 promoters in S. cerevisiae, 17 probably have class 2 promoters in one or more other species. Conversely, among 322 genes which very likely have class 2 promoters in S. cerevisiae, 44 probably have class 1 promoters in one or more other species. Also, for at least 2 genes from the set of 212 S. cerevisiae genes with class 1 promoters, the locations of the TATA consensus sequences are substantially different between the species.

Conclusion
Our results indicate that, in the course of yeast evolution, a promoter switches its class with the probability at least ~0.1 per time required for the accumulation of one nucleotide substitution at a non-coding site. Thus, key sequences involved in initiation of transcription evolve with substantial rates in yeast.
Highly expressed proteins have an increased frequency of alanine in the second amino acid position
Authors: Tats Age , Remm Maido , Tenson Tanel 
Published: February 2006

Abstract

Background
Although the sequence requirements for translation initiation regions have been frequently analysed, usually the highly expressed genes are not treated as a separate dataset.

Results
To investigate this, we analysed the mRNA regions downstream of initiation codons in nine bacteria, three archaea and three unicellular eukaryotes, comparing the dataset of highly expressed genes to the dataset of all genes. In addition to the detailed analysis of the nucleotide and codon frequencies we compared the N-termini of highly expressed proteins to the N-termini of all proteins coded in the genome.

Conclusion
The most conserved pattern was observed at the amino acid level: strong alanine over-representation was observed at the second amino acid position of highly expressed proteins. This pattern is well conserved in all three domains of life.
Cytokine responses of bovine macrophages to diverse clinical Mycobacterium avium subspecies paratuberculosis strains
Authors: Janagama Harish K , il Jeong Kwang , Kapur Vivek , Coussens Paul , Sreevatsan Srinand 
Published: February 2006

Abstract

Background

Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne's disease (JD) persistently infects and survives within the host macrophages. While it is established that substantial genotypic variation exists among MAP, evidence for the correlates that associate specific MAP genotypes with clinical or sub-clinical disease phenotypes is presently unknown. Thus we studied strain differences in intracellular MAP survival and host responses in a bovine monocyte derived macrophage (MDM) system.

Results
Intracellular survival studies showed that a bovine MAP isolate (B1018) and a human MAP isolate (Hu6) persisted in relatively higher numbers when compared with a sheep MAP isolate (S7565) at 24-hr, 48-hr and 96-hr post infection (PI). MDMs stimulated with B1018 up-regulated IL-10 at the transcript level and down-regulated TNFα at the protein and transcript levels compared with stimulations by the S7565 and Hu6. MDMs infected with Hu6 showed a down regulatory pattern of IL-10 and TNFα compared to stimulations by S7565. Cells stimulated with B1018 and Hu6 had low levels of matrix metalloprotease-3 (MMP3) and high levels of tissue inhibitor of metalloprotease-1 (TIMP1) at 96-hr PI relative to MDMs stimulated by S7565.

Conclusion
Taken together, results suggest that the bovine (B1018) and the human (Hu6) MAP isolates lead to anti-inflammatory and anti-invasive pathways in the macrophage environment whereas the sheep (S7565) MAP isolate induces a pro-inflammatory pathway. Thus the infecting strain genotype may play a role in polarizing the host immune responses and dictate the clinicopathological outcomes in this economically important disease.
Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments
Authors: Scintu Franca , Reali Camilla , Pillai Rita , Badiali Manuela , Sanna Maria Adele , Argiolu Francesca , Ristaldi Maria Serafina , Sogos Valeria 
Published: February 2006

Abstract

Background
It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential.

Results
In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC). Cells were treated with: (1) TPA, forskolin, IBMX, FGF-1 or (2) retinoic acid and 2-mercaptoethanol (BME). Treatment (1) induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1) compared with treatment (2). In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments.

Conclusion
Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.