bluuebunny/crossref_metadata_2025 huggingface dataset:
IP-10 Blocks Vascular Endothelial Growth Factor-Induced Endothelial Cell Motility and Tube Formation via Inhibition of Calpain
Authors: Bodnar Richard J. , Yates Cecelia C. , Wells Alan
Published: February 2006

Angiogenesis plays a critical role in wound repair. Endothelial cells present CXC receptor 3 (CXCR3) for chemokines expressed late in wound regeneration. To understand the physiological role CXCR3 plays in regulating endothelial function, we analyzed the ability of a CXCR3 ligand, IP-10 (CXCL10), to influence endothelial cell tube formation. Treatment of endothelial cells with IP-10 in the presence of vascular endothelial growth factor (VEGF) inhibited tube formation on growth factor-reduced Matrigel and in a subcutaneous Matrigel plug. Furthermore, IP-10 significantly inhibited VEGF-induced endothelial motility, a response critical for angiogenesis. Previous work showed that CXCR3 ligandation initiates protein kinase A (PKA) phosphorylation-dependent inhibition of m-calpain, required for induced cell motility, in fibroblasts but not epithelial cells. Here we show that CXCR3 activation in endothelial cells induces an increase in cAMP and PKA activation. Treatment of endothelial cells with Rp-8-Br-cAMP, an inhibitor of PKA, or small interference RNA to PKA was able to reverse the inhibitory effects of IP-10 on VEGF-mediated tube formation and motility. Importantly, treatment of endothelial cells with VEGF induced the activation of m-calpain, but costimulation with IP-10 significantly decreased this activity. Using Rp-8-Br-cAMP, we show blocking PKA reversed the IP-10 inhibition of VEGF-induced m-calpain activity. These data indicate that the activation of CXCR3 inhibits endothelial tube formation through a PKA mediated inhibition of m-calpain. This provides a means by which late wound repair signals limit the angiogenesis driven early in the wound response process.
The Markers of Habitual Aspect in English
Authors: Binnick Robert I.
Published: February 2006

Contrary to the traditional account of habitual aspect in English, the only marker of habituality is will, with its past tense, would. Used tofunctions as a kind of anti-presentperfect tense, contrasting past states of affairs with present ones. In certain contexts, various tenses, and not merely the simple ones, may receive habitual interpretations, but these are not their meanings. Generic readings are contextual interpretations; there are no markers of generic aspect in English.
Recent advances in the study of development, social and personal experience, and psychopathology
Authors: Bukowski William M. , Adams Ryan E. , Santo Jonathan B.
Published: February 2006

The field of developmental psychopathology has been challenged by various issues in understanding the link between social experiences and psychopathology. These challenges involve conceptual, methodological and statistical concerns that are often interrelated. This article examines four advances in resolving these concerns. First, co-rumination and deviancy training are discussed as specific interpersonal processes that are examples of important social experiences for predicting psychopathology. Second, dynamic properties of dyadic interaction are discussed as one of the recent advances in methodology for this area. Third, the Actor-Partner Interdependence Model is outlined as one of the recent statistical advances in the study of individuals within a dyad. Fourth, changes in the study of culture are presented as informing the understanding link between social experiences and developmental psychopathology.
Developmental psychopathology: Pathways to the future
Authors: Masten Ann S.
Published: February 2006

This article highlights the defining principles, progress and future directions in developmental psychopathology in relation to this special section. Six fundamental principles of developmental psychopathology are identified and the pervasive impact of this integrative framework on research, theory, and practice in behavioral health fields over the past three decades is described. This special section reflects the increasing influence of developmental systems theory, the growing focus on change, intensifying interest in translational research, and the increasingly complex and differentiated nature of research on pathways toward and away from psychopathology. A new era in developmental psychopathology is dawning, with exciting frontiers in brain development and plasticity, gene-environment interaction, resilience and recovery, multilevel dynamics, interdisciplinary research and training, and methodologies for assessing and analyzing change over time within and across individual systems and their contexts.
Toward Theory-Led Evaluation
Authors: Molas-Gallart Jordi , Davies Andrew
Published: February 2006

This article reviews the literature and practice concerned with the evaluation of science, technology, and innovation (STI) policies and theway these relate to theories of the innovation process. Referring to the experience of the European Union (EU), the authors review the attempts to ensure that the STI policy theory is informed by advances in the authors'understanding of the innovation process. They argue, however, that the practice of policy evaluation lags behind advances in innovation theory. Despite the efforts to promote theory-led evaluations of STI policies based on new theories of the systemic nature of innovation, evaluation practice in the EU continues to favor the development of methods implicitly based on outdated linear views of the innovation process. This article examines the reasons why this is the case and suggests that STI policy evaluation should nevertheless be supported by the evolving theoretical understanding of the innovation process.
Effect of cerium sulphide particle dispersions on acicular ferrite microstructure development in steels
Authors: Thewlis G.
Published: February 2006

Of the phases found in wrought steels, cerium sulphide particles are notable in that they can be both stable at liquid metal temperatures and exhibit good lattice coherency with α iron. An investigation has been carried out to determine the effectiveness of cerium sulphide particle dispersions in nucleating intragranular acicular ferrite microstructures in steels. Vacuum melts of 50 kg have been manufactured of appropriate base steel compositions with varying additions of cerium (0·04–0·18%) and sulphur (0·01–0·04%). The work has shown that 0·02–0·12% cerium and 70–340 ppm sulphur may be retained in steels after deoxidation and desulphurisation reactions while oxygen can be reduced to <20 ppm. Resulting inclusions are largely spheroidal in shape and consist of several crystalline compounds, notably CeS, Ce3S4 and Ce2O2S. The inclusion numbers are of the order of 0·68–6·12 × 106 mm−3 with mean diameters of 0·63–1·70 μm. The densities of these inclusion dispersions are approaching those in weld metals where acicular ferrite is the dominant microstructure constituent. Significant volume fractions of acicular ferrite (up to 65%) have been obtained in steels after thermally cycling in a dilatometer and cooling at rates simulating transformation conditions ranging from high heat input welding to air cooling of forgings and water cooling of plate. A potential beneficial effect of acicular ferrite on mechanical properties in high heat input welding (heat affected zone grain refinement) and in thermo-mechanically processed steels (relaxed schedules) has been highlighted. A pilot plant billet cast of steel has shown the feasibility of achieving the required particle dispersions and acicular ferrite microstructure in tonnage steelmaking.
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.
Effect of heat treatment on tensile properties of friction stir welded joints of 2219-T6 aluminium alloy
Authors: Liu H. J. , Chen Y. C. , Feng J. C.
Published: February 2006

The effect of post-weld heat treatment (PWHT) on the tensile properties of friction stir welded (FSW) joints of 2219-T6 aluminium alloy was investigated. The PWHT was carried out at aging temperature of 165°C for 18 h. The mechanical properties of the joints were evaluated using tensile tests. The experimental results indicate that the PWHT significantly influences the tensile properties of the FSW joints. After the heat treatment, the tensile strength of the joints increases and the elongation at fracture of the joints decreases. The maximum tensile strength of the joints is equivalent to 89% of that of the base material. The fracture location characteristics of the heat treated joints are similar to those of the as welded joints. The defect free joints fracture in the heat affected zone on the retreating side and the joints with a void defect fracture in the weld zone on the advancing side. All of the experimental results can be explained by the hardness profiles and welding defects in the joints.
Friction and wear behaviour of β-silicon nitride–steel couples under unlubricated conditions
Authors: Reis P. , Davim J. P. , Xu X. , Ferreira J. M. F.
Published: February 2006

The friction and wear behaviour of colloidally processed and pressureless sintered β-silicon nitride (Si3N4) ceramics against steel DIN Ck45K under unlubricated condition were investigated using a pin on disk tribometer. β-silicon nitride (Si3N4) ceramics consolidated by slip casting from suspensions with different solid loading have been studied, aiming at increasing the use of β-Si3N4 as cutting tools in industrial applications. The morphology of the worn surfaces of β-silicon nitride ceramics was analysed by scanning electron microscopy (SEM) and energy dispersion spectroscopy (EDS). Under the conditions used, it was found that β-Si3N4 ceramics exhibited a low wear rate (10−6 mm3 N−1 m−1) and the frictional behaviour of β-Si3N4 ceramics–steel couples depended on a metallic layer transferred from the steel disk to the β-Si3N4 ceramic pin.
Investigation of Fe2O3–Al and Cr2O3–Al reactions using a high speed video camera
Authors: Menekse O. , Wood J. V. , Riley D. S.
Published: February 2006

Self propagating high temperature synthesis is a simple, fast and energy efficient process with a wide range of applications, one of which is the coating of the internal surfaces of steel pipes using a centrifugal thermit process. The process involves a highly exothermic reaction between powder reactants distributed around a steel tube rotating at high speed. Although the process has been widely studied, important features, particularly how the reaction propagates, have not been completely revealed due to extremely high reaction rates and temperatures. In the present work, Fe2O3–Al and, to a lesser degree, Cr2O3–Al reactions were studied under stationary (non-rotating) and rotating conditions using a high speed video camera by which the centrifugal thermit process was, for the first time, recorded optically. Video recordings clearly demonstrate that, in contradiction to current belief, the reaction does not always propagate in a well ordered (spiral) pattern, but involves multiple, randomly distributed ignition sites.
Microstructure and wear properties of TiC–VC reinforced iron based hardfacing layers
Authors: Wang X. H. , Zhang M. , Zou Z. D. , Qu S. Y.
Published: February 2006

TiC–VC reinforced Fe based hardfacing layers were obtained by shielded manual arc welding (SMAW) of which H08A rare electrodes were coated by different amounts of ferrotitanium (FeTi), ferrovanadium (FeV) and graphite. The microstructure of the hardfacing layers was investigated by means of scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electron probe microanalysis (EPMA). The thermodynamics and effect of elements on the carbides were also discussed. It was shown that TiC–VC carbides could be formed during arc welding. The composition and amount of flux evidently affect the microstructure and properties of the coatings. Good crack resistance and higher hardness of the harfacing layer could be obtained, while the amounts of graphite, FeTi and FeV were controlled within a range of 8–10%, 15–18% and 8–12% respectively. TiC–VC reinforced Fe based hardfacing layers possess much greater wear resistance and a smaller friction coefficient than 1045 steel substrate.
Temperature distribution and residual stresses during multipass narrow gap welding of thick plates
Authors: Xu J. J. , Zhu Z. Q. , Chen L. G. , Ni C. Z.
Published: February 2006

In a multipass welding operation, the temperature distribution and residual stresses developed in the material change with each weld pass, and are therefore more complicated than those of single-pass welding. In the present study, two methods – testing and finite element analysis (FEA) – were used to determine the temperature distribution in thick plate with narrow gap during multipass submerged arc welding (SAW). The residual stresses on the top surface, bottom surface and along the thickness direction at some distance away from the weld line are presented. The results are compared with those calculated by FEA. These are used to validate the finite element model which is then used to appraise the weld performance.
Assessment of surface bonding strength in Al clad steel strip using electrical resistivity and peeling tests
Authors: Manesh H. Danesh
Published: February 2006

Aluminium clad steel strip successfully combines the surface properties of an aluminium alloy coating with the satisfactory mechanical properties of the steel substrate. The production of Al clad steel strip by rolling, however, is a more efficient and economical approach compared with other processes. In this investigation, trilayer strips of aluminium/steel/aluminium were produced using the cold roll bonding technique. The bonding strength between the layers and the electrical resistivity of the samples were measured using a peeling test and four point probe test, respectively. The effects of reduction of thickness, the friction condition between the outer layer and rolls, and the rolling velocity on the bonding strength and electrical resistivity of the samples were assessed. Finally, it is shown that the resistivity test can be used as a non-destructive test for the evaluation of the quality of bonding between the layers of aluminium clad steel strip.
Fracture criterion for hydrogen embrittlement of high strength steel
Authors: Wang M.-Q. , Akiyama E. , Tsuzaki K.
Published: February 2006

The notch tensile strength of a boron bearing steel at 1305 MPa has been investigated by means of slow strain rate tests after electrochemical hydrogen charging. Results show that the notch tensile strength of the steel decreased with increasing diffusible hydrogen content and the decrease in the notch tensile strength was more pronounced for specimens at a higher stress concentration factor. Finite element analysis results show that the dependence of the notch tensile strength on stress concentration factor cannot be accounted for by the local peak stress and local peak hydrogen concentration; however, the equivalent plastic strain at the notch root at an applied stress equal to the notch tensile strength was independent of stress concentration factor. The equivalent plastic strain at the notch root can be used as a fracture criterion for hydrogen embrittlement of the steel.
Damage tolerance of nanolayer grained ceramics and quantitative estimation
Authors: Bao Y. W. , Hu C. F. , Zhou Y. C.
Published: February 2006

In order to meet increasing requirement for the evaluation and design of damage tolerance of brittle materials, a simple expression was proposed to estimate the damage tolerance quantitatively using basic material parameters, based on the features of damage tolerance and fracture mechanics. The calculated results from this equation indicated that the damage tolerance of nanolayer grained ceramics was over 10 times higher than that of some brittle ceramics, while glass has the lowest damage tolerance. Therefore, the damage tolerance of various ceramics can be estimated directly using their basic properties data without the necessity of additional tests. SEM examination and finite element simulation showed that the high damage tolerance of the layer grained ceramics was attributed to delamination in grains, interlocking microstructures and crack deflection.
Fabrication and machinability of Si3N4–Mg–Al–Zn (AZ91) composites
Authors: Wang S. R. , Geng H. R. , Wang Y. Z.
Published: February 2006

Two Si3N4–Mg–Al–Zn (AZ91) metal matrix composites (MMCs) were fabricated by immersing, sintering and infiltration processes. The cutting tool materials and cutting parameter had an important influence on the lathe turning properties of Si3N4–Mg–Al–Zn composites. The machinability changed along with the distribution and volume fractions of reinforcement. The cutting material polycrystalline diamond (PCD) is one of the optimal materials to machine MMCs. The surface roughness of Si3N4–Mg–Al–Zn composites decreased with increasing cutting velocity at first, then increased with increasing cutting velocity owing to Si3N4 ceramic phase participating in cutting, and the surface roughness linearly increased along with the increase in feed rate of not only Mg–Al–Zn alloy but also Si3N4–Mg–Al–Zn composites, whereas the cutting depth had very little effect on surface roughness. The difference in machinability between Si3N4–Mg–Al–Zn composites and Mg–Al–Zn alloy was large.
Coordination of erythropoiesis by the transcription factor c-Myb
Authors: Vegiopoulos Alexandros , García Paloma , Emambokus Nikla , Frampton Jon
Published: February 2006

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

The 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

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

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

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

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

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

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

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

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

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

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.
Molecular characterization and differential expression of cytokinin-responsive type-A response regulators in rice (Oryza sativa)
Authors: Jain Mukesh , Tyagi Akhilesh K , Khurana Jitendra P
Published: February 2006

Background

The response regulators represent the elements of bacterial two-component system and have been characterized from dicot plants like Arabidopsis but little information is available on the monocots, including the cereal crops. The aim of this study was to characterize type-A response regulator genes from rice, and to investigate their expression in various organs as well as in response to different hormones, including cytokinin, and environmental stimuli.

Results

By analysis of the whole genome sequence of rice, we have identified ten genes encoding type-A response regulators based upon their high sequence identity within the receiver domain. The exon-intron organization, intron-phasing as well as chromosomal location of all the RT-PCR amplified rice (Oryza sativa) response regulator (OsRR) genes have been analyzed. The transcripts of OsRR genes could be detected by real-time PCR in all organs of the light- and dark-grown rice seedlings/plants, although there were quantitative differences. The steady-state transcript levels of most of the OsRR genes increased rapidly (within 15 min) on exogenous cytokinin application even in the presence of cycloheximide. Moreover, the expression of the OsRR6 gene was enhanced in rice seedlings exposed to salinity, dehydration and low temperature stress.

Conclusion

Ten type-A response regulator genes identified in rice, the model monocot plant, show overlapping/differential expression patterns in various organs and in response to light. The induction of OsRR genes by cytokinin even in the absence of de novo protein synthesis qualifies them to be primary cytokinin response genes. The induction of OsRR6 in response to different environmental stimuli indicates its role in cross-talk between abiotic stress and cytokinin signaling. These results provide a foundation for further investigations on specific as well as overlapping cellular functions of type-A response regulators in rice.
EST analysis of the scaly green flagellate Mesostigma viride (Streptophyta): Implications for the evolution of green plants (Viridiplantae)
Authors: Simon Andreas , Glöckner Gernot , Felder Marius , Melkonian Michael , Becker Burkhard
Published: February 2006

Background

The Viridiplantae (land plants and green algae) consist of two monophyletic lineages, the Chlorophyta and the Streptophyta. The Streptophyta include all embryophytes and a small but diverse group of freshwater algae traditionally known as the Charophyceae (e.g. Charales, Coleochaete and the Zygnematales). The only flagellate currently included in the Streptophyta is Mesostigma viride Lauterborn. To gain insight into the genome evolution in streptophytes, we have sequenced 10,395 ESTs from Mesostigma representing 3,300 independent contigs and compared the ESTs of Mesostigma with available plant genomes (Arabidopsis, Oryza, Chlamydomonas), with ESTs from the bryophyte Physcomitrella, the genome of the rhodophyte Cyanidioschyzon, the ESTs from the rhodophyte Porphyra, and the genome of the diatom Thalassiosira.

Results

The number of expressed genes shared by Mesostigma with the embryophytes (90.3 % of the expressed genes showing similarity to known proteins) is higher than with Chlamydomonas (76.1 %). In general, cytosolic metabolic pathways, and proteins involved in vesicular transport, transcription, regulation, DNA-structure and replication, cell cycle control, and RNA-metabolism are more conserved between Mesostigma and the embryophytes than between Mesostigma and Chlamydomonas. However, plastidic and mitochondrial metabolic pathways, cytoskeletal proteins and proteins involved in protein folding are more conserved between Mesostigma and Chlamydomonas than between Mesostigma and the embryophytes.

Conclusion

Our EST-analysis of Mesostigma supports the notion that this organism should be a suitable unicellular model for the last flagellate common ancestor of the streptophytes. Mesostigma shares more genes with the embryophytes than with the chlorophyte Chlamydomonas reinhardtii, although both organisms are flagellate unicells. Thus, it seems likely that several major physiological changes (e.g. in the regulation of photosynthesis and photorespiration) took place early during the evolution of streptophytes, i.e. before the transition to land.
Randomised controlled trial of cervical radiofrequency lesions as a treatment for cervicogenic headache [ISRCTN07444684]
Authors: Haspeslagh Sara RS , Van Suijlekom Hans A , Lamé Inge E , Kessels Alfons GH , van Kleef Maarten , Weber Wim EJ
Published: February 2006

Background

Cervicogenic headache (CEH) is a unilateral headache localised in the neck or occipital region, projecting to the frontal and temporal regions. Since the pathogenesis of this syndrome appears to have an anatomical basis in the cervical region, several surgical procedures aimed at reducing the nociceptive input on the cervical level, have been tested. We developed a sequence of various cervical radiofrequency neurotomies (facet joint denervations eventually followed by upper dorsal root ganglion neurotomies) that proved successful in a prospective pilot trial with 15 CEH patients. To further evaluate this sequential treatment program we conducted a randomised controlled trial

Methods

30 patients with cervicogenic headache according to the Sjaastad diagnostic criteria, were randomised. 15 patients received a sequence of radiofrequency treatments (cervical facet joint denervation, followed by cervical dorsal root ganglion lesions when necessary), and the other 15 patients underwent local injections with steroid and anaesthetic at the greater occipital nerve, followed by transcutaneous electrical nerve stimulation (TENS) when necessary. Visual analogue scores for pain, global perceived effects scores, quality of life scores were assessed at 8, 16, 24 and 48 weeks. Patients also kept a headache diary.

Results

There were no statistically significant differences between the two treatment groups at any time point in the trial.

Conclusion

We did not find evidence that radiofrequency treatment of cervical facet joints and upper dorsal root ganglions is a better treatment than the infiltration of the greater occipital nerve, followed by TENS for patients fulfilling the clinical criteria of cervicogenic headache.
Searching for observational studies: what does citation tracking add to PubMed? A case study in depression and coronary heart disease
Authors: Kuper Hannah , Nicholson Amanda , Hemingway Harry
Published: February 2006

Background

PubMed is the most widely used method for searches of the medical literature, but fails to identify many relevant articles. Electronic citation tracking offers an alternative search method.

Methods

Articles investigating the role of depression in the aetiology and prognosis of coronary heart disease were sought through two methods: a) PubMed, and b) citation tracking where Science Citation Index was searched for all articles which cited ("forward citation tracking") or were cited by ("backward citation tracking") any of the articles in an index review. The number and quality of eligible articles identified by the two methods were compared.

Results

50 articles that were not already included in the index review met our inclusion criteria; 11 were identified through Science Citation Index alone, 8 through PubMed alone, and 31 through both methods. Articles identified by Science Citation Index alone were published in higher impact factor journals, were larger and were less likely to show a positive association.

Conclusion

Science Citation Index identified more eligible articles than PubMed, and these differed qualitatively. Failing to use citation tracking in a systematic review of observational studies may result in bias.