bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic intervention of transcription for identifying network response to disease and cellular phenotypes
Authors: Li Huai , Zhan Ming 
Published: November 2005

Abstract
Motivation: A major challenge in post-genomic research has been to understand how physiological and pathological phenotypes arise from the networks of expressed genes. Here, we addressed this issue by developing an algorithm to mimic the behavior of regulatory networks in silico and to identify the dynamic response to disease and changing cellular conditions.
Results: With regulatory pathway and gene expression data as input, the algorithm provides quantitative assessments of a wide range of responses, including susceptibility to disease, potential usefulness of a given drug, or consequences to such external stimuli as pharmacological interventions or caloric restriction. The algorithm is particularly amenable to the analysis of systems that are difficult to recapitulate in vitro, yet they may have important clinical value. The hypotheses derived from the algorithm were biologically relevant and were successfully validated via independent experiments, as illustrated here in the analysis of the leukemia-associated BCR–ABL pathway and the insulin/IGF pathway related to longevity. The algorithm correctly identified the leukemia drug target and genes important for longevity, and also provided new insights into our understanding of these two processes.
Availability: The software package is available upon request to the authors.
Contact:
Supplementary information: Supplementary data are available at Bioinformatics online.
Simplification and its consequences in biological modelling: conclusions from a study of calcium oscillations in hepatocytes
Authors: Hetherington James P.J , Warner Anne , Seymour Robert M 
Published: November 2005

Systems Biology requires that biological modelling is scaled up from small components to system level. This can produce exceedingly complex models, which obscure understanding rather than facilitate it. The successful use of highly simplified models would resolve many of the current problems faced in Systems Biology. This paper questions whether the conclusions of simple mathematical models of biological systems are trustworthy. The simplification of a specific model of calcium oscillations in hepatocytes is examined in detail, and the conclusions drawn from this scrutiny generalized. We formalize our choice of simplification approach through the use of functional ‘building blocks’. A collection of models is constructed, each a progressively more simplified version of a well-understood model. The limiting model is a piecewise linear model that can be solved analytically.We find that, as expected, in many cases the simpler models produce incorrect results. However, when we make a sensitivity analysis, examining which aspects of the behaviour of the system are controlled by which parameters, the conclusions of the simple model often agree with those of the richer model. The hypothesis that the simplified model retains no information about the real sensitivities of the unsimplified model can be very strongly ruled out by treating the simplification process as a pseudo-random perturbation on the true sensitivity data. We conclude that sensitivity analysis is, therefore, of great importance to the analysis of simple mathematical models in biology. Our comparisons reveal which results of the sensitivity analysis regarding calcium oscillations in hepatocytes are robust to the simplifications necessarily involved in mathematical modelling. For example, we find that if a treatment is observed to strongly decrease the period of the oscillations while increasing the proportion of the cycle during which cellular calcium concentrations are rising, without affecting the inter-spike or maximum calcium concentrations, then it is likely that the treatment is acting on the plasma membrane calcium pump.
Interactions between the Cell Cycle and Embryonic Patterning inArabidopsisUncovered by a Mutation in DNA Polymerase ε
Authors: Jenik Pablo D. , Jurkuta Rebecca E.J. , Barton M. Kathryn 
Published: November 2005

AbstractPattern formation and morphogenesis require coordination of cell division rates and orientations with developmental signals that specify cell fate. A viable mutation in the TILTED1 locus, which encodes the catalytic subunit of DNA polymerase ε of Arabidopsis thaliana, causes a lengthening of the cell cycle by ∼35% throughout embryo development and alters cell type patterning of the hypophyseal lineage in the root, leading to a displacement of the root pole from its normal position on top of the suspensor. Treatment of preglobular and early globular stages, but not later stage, embryos with the DNA polymerase inhibitor aphidicolin leads to a similar phenotype. The results uncover an interaction between the cell cycle and the processes that determine cell fate during plant embryogenesis.
Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season
Authors: Onbasi K. , Sin A. Z. , Doganavsargil B. , Onder G. F. , Bor S. , Sebik F. 
Published: November 2005

SummaryBackground
The oesophagus is normally devoid of eosinophils. There are some disorders accompanying with eosinophil infiltration. Food allergy has been reported as a common reason, especially in children but some other studies have also indicated that aeroallergens might have a role in oesophageal eosinophil accumulation.Objective
In this study we investigated whether there is any eosinophil recruitment in the oesophagus of pollen‐allergic patients who had respiratory symptoms during the season.Methods
Thirty‐eight symptomatic patients (allergic rhinitis (AR) with or without asthma) who had sensitization to grass pollen were included in the study during the pollen season. Controls were composed of 25 healthy non‐atopics and 24 patients diagnosed as having gastro‐oesophageal reflux disease. Reflux was excluded in allergic and non‐atopic groups, whereas the presence of allergy was eliminated in control groups. Gastrointestinal endoscopy was performed in all participants, and biopsy specimens were taken from both the proximal and the distal oesophagus to evaluate eosinophil accumulation. At the same time, blood eosinophil numbers were counted.Results
Oesophageal eosinophil accumulation was found in 10 allergic patients (26%) and in five patients (21%) with gastro‐oesophageal reflux disease but none of the healthy controls had eosinophils (0%) (P<0.05). Blood eosinophils were higher in these 10 patients than the rest of the 28 patients without infiltration. In this group, blood eosinophils were also correlated with the number of accumulated eosinophils in the oesophagus (P<0.001). There was more intense eosinophil infiltration at the distal part of the oesophagus in the reflux group when compared with the allergic group (mean 7.6±5.6 vs. 3.2±3.7). Nevertheless, eosinophils were found to be concentrated (mean 5.5±7.3) in the proximal oesophagus of allergic patients, although it was 1.7±1.5 in reflux patients (P>0.05).Conclusion
Our results showed that eosinophil infiltration might be observed in oesophageal tissue of patients with respiratory tract allergy during the symptomatic period. This finding may possibly reflect the systemic and common mucosal aspects of allergic inflammation.
Patterns of food allergen‐specific cytokine production by T lymphocytes of children with multiple allergies
Authors: Scott‐Taylor T. H. , Hourihane J. B. , Harper J. , Strobel S. 
Published: November 2005

AbstractBackground
The contribution of different T cell subsets to the overall measured cytokine response to food allergens is largely unexplored.Method
The patterns of cytokine production of peripheral blood‐derived T cells after allergen stimulation were studied in 22 children with multiple food allergies and in 20 non‐allergic children as controls, using flow cytometry.Results
Proportions of T cells of food‐sensitized children spontaneously secreting IFN‐γ and IL‐10 (without antigen stimulation) were lower than non‐atopic children and adult controls (P0.001). The proportions of IL‐4‐producing cells in vitro were significantly increased (P0.04) and IFN‐γ‐producing cells were significantly reduced (P0.05) in sensitized children after incubation with and without dendritic cell presentation of peanut extract, β‐lactoglobulin and ovalbumin. The reverse pattern was found in non‐sensitized children and adult controls. IL‐4 secretion in allergic children to sensitizing allergens was mainly restricted to the CD4+ CD45 RO+ population while in non‐atopic controls both CD4+ and CD8+ CD45 RO+ cells produced mostly IFN‐γ. Food‐specific IgE values did not correspond with cytokine responses but IL‐4 production and IFN‐γ reduction relative to normal children were closely associated with total IgE levels.Conclusion
Food‐allergic children's IL‐4 cytokine response to their relevant allergens is predominantly from a memory population of CD4+ CD45 RO+ cells, whereas IL‐4 and IFN‐γ secretion of non‐allergic controls was predominantly from mixed CD4+ and CD8+ CD45 RO+ populations.
Markers of platelet activation in plasma of patients suffering from persistent allergic rhinitis with or without asthma symptoms
Authors: Kasperska‐Zając A. , Rogala B. 
Published: November 2005

SummaryBackground
Increased circulating levels of platelet release products are detected in various types of inflammation. It has been demonstrated that allergen challenge promotes platelet activation and leads to the release of chemokines such as platelet factor 4 (PF‐4) and β‐thromboglobulin (β‐TG).Objective
The aim of this study was to determine whether or not circulating platelets get into an activated state during allergic inflammatory reactions induced by long‐term natural exposure to allergens.Methods
Plasma levels of PF‐4 and β‐TG (established markers of in vivo platelet activation) were determined by ELISA method in symptomatic patients with allergy to house dust mites, suffering from persistent allergic rhinitis (PAR) in the absence of asthma symptoms (12 men and 8 women; mean age 22 years) and from PAR with mild asthma (10 men and 6 women; mean age 23 years), as well as in healthy controls (10 men and 10 women; mean age 23 years).Results
No significant differences were found between PAR patients with or without symptoms of asthma and healthy non‐atopic subjects with respect to plasma levels of PF‐4 and β‐TG as well as platelet count.Conclusions
It seems that patients undergoing continuous natural exposure to sensitizing allergens, with subsequent PAR alone or with concomitant mild asthma, have no altered platelet activity in vivo, as reflected by plasma levels of the chemokines. These findings, in conjunction with earlier data, indicate that differences may exist in platelet activity, including releasability of platelet products between patients with distinct clinical manifestation of atopy.
Wheezing in Chinese schoolchildren: disease severity distribution and management practices, a community‐based study in Hong Kong and Guangzhou
Authors: Ko F. W. S. , Wang H. Y. , Wong G. W. K. , Leung T. F. , Hui D. S. C. , Chan D. P. S. , Zhong N. S. , Lai C. K.W. 
Published: November 2005

SummaryBackground
Asthma is a common chronic disease and information on its management practices at the community level is helpful in identifying problems and improving asthma care.Objective
To assess the severity status and management of the asthma symptom of wheeze of children at the community level in Hong Kong (HK) and Guangzhou (GZ).Methods
Cross‐sectional study of children aged 10 years using the International Study of Asthma and Allergic disease in Childhood (ISAAC Phase II protocol). Asthma management and lung function were assessed in 178 (98 from HK and 80 from GZ) randomly selected children with wheeze over the past 12 months.Results
Eighty‐three percent, 11%, 6% and 0% of children suffered from intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively, according to the frequency of their symptoms. Addition of spirometric parameter only changed the asthma severity classification in 2.8% of children. Medications were used by 30.6% and 71.3% of children for wheeze in HK and GZ, respectively. In HK, inhaled β2‐agonist (73.3% among the drug users) was the commonest medication used followed by inhaled corticosteroid (ICS) (23.3%). In GZ, inhaled β2‐agonist was used by 75.4% of children, but use of ICS (26.3%), oral β2‐agonist (26.3%), oral theophylline (45.6%), oral ketotifen (36.8%) and oral steroid (35.1%) were also common. ICS was only used by 11.4% of children with persistent asthma. Ten percent and 18.7% of children in HK and GZ, respectively, had emergency department visits, while 16.3% and 11.6% of children in HK and GZ, respectively, had missed school secondary to asthma over the past 1 year.Conclusions
Most children in the community had intermittent asthma and addition of lung function to symptoms did not significantly affect classification of asthma severity. Significant morbidity was seen even in this group of children with mostly intermittent and mild persistent asthma.
Identification of strong interleukin‐10 inducing lactic acid bacteria which down‐regulate T helper type 2 cytokines
Authors: Niers L. E. M. , Timmerman H. M. , Rijkers G. T. , van Bleek G. M. , van Uden N. O. P. , Knol E. F. , Kapsenberg M. L. , Kimpen J. L. L. , Hoekstra M. O. 
Published: November 2005

SummaryBackground
Decreased exposure to microbial stimuli has been proposed to be involved in the increased prevalence of atopic disease. Such a relationship was indicated by enhanced presence of typical probiotic bacteria in the intestinal flora correlating with reduced prevalence of atopic disease. Recent clinical trials suggested that probiotic bacteria may decrease and prevent allergic symptoms, but which (different) species or strains may contribute is poorly understood.Objective
We sought to select probiotic bacteria by their ability to modulate in vitro production of cytokines by peripheral blood mononuclear cells (PBMCs), to make a rational choice from available strains.Methods
PBMCs, purified monocytes, and lymphocytes from healthy donors were co‐cultured with 13 different strains of probiotic bacteria. The effect of lactic acid bacteria (LAB) on different cell populations and effects on cytokine production induced by the polyclonal T cell stimulator phytohaemagglutinin (PHA) was evaluated by measuring T helper type 1, T helper type 2 (Th2), and regulatory cell cytokines in culture supernatants by multiplex assay.Results
PBMCs cultured with different strains produced large amounts of IL‐10 and low levels of IL‐12p70, IL‐5, and IL‐13. In PHA‐stimulated PBMC cultures, the tested strains decreased the production of Th2 cytokines. Neutralizing IL‐10 production resulted in partial to full restoration of Th2 cytokine production and concurred with an increase in pro‐inflammatory cytokines such as IL‐12p70 and TNF‐α. Within the PBMCs, the CD14+ cell fraction was the main source of IL‐10 production upon interaction with LAB.Conclusion
Our results indicate that certain strains of lactobacilli and bifidobacteria modulate the production of cytokines by monocytes and lymphocytes, and may divert the immune system in a regulatory or tolerant mode. These specific strains may be favorable to use in prevention or treatment of atopic disease.
Intensive sampling and transplantation experiments reveal continued effects of episodic acidification on sensitive stream invertebrates
Authors: KOWALIK RENATA A. , ORMEROD S. J. 
Published: November 2005

Summary1. Although mean pH is increasing in acidified streams throughout Europe, benthic invertebrates are recovering only slowly. One developing hypothesis is that acid episodes continue to restrict recolonisation and recovery. Here, we used intra‐annual sampling in replicate circumneutral, acid and episodic streams at the Llyn Brianne experimental catchments to assess possible mayfly exposure to episodic effects quantified from a risk index based on long‐term discharge. Episodic effects were then tested using short‐term transplantations of animals in enclosures.2. No mayflies occurred in acid streams while Baetis rhodani occurred in episodic streams but declined to zero density following low pH in autumn. Ephemerella ignita, Baetis vernus, B. muticus, Rhithrogena semicolorata, Ecdyonurus spp. and Heptagenia lateralis occurred only in the circumneutral streams. The first two species were present as nymphs only during July and August so that episodic exposure risk was minimal, but the remaining species occurred as nymphs in all months.3. Baetis rhodani transplanted during base‐flow (September 2003) and high‐flow (April 2004) were exposed to either; (i) continual (chronic) exposure in the acid streams over 16 days or (ii) repeated short‐term (episodic) exposure to acid conditions for 2 × 4 day periods interspersed with 4‐day recovery periods in the circumneutral streams. Baetis survival in the circumneutral streams (always pH > 5.7) remained high during both low‐ and high‐flow. By comparison, mortality increased (P < 0.01) during chronic and episodic exposure, but only during high‐flow (mean pH 3.8–3.9, cf. 5.5–5.8 at low flow) when mortality varied significantly in the order chronic (>80%) > episodic (>40%) >circumneutral (<10%).4. We conclude that, despite Europe‐wide trends towards chemical recovery from acidification, even short exposures to high‐flow events at Llyn Brianne are still sufficiently acid to reduce the survival of B. rhodani. Most mayfly species absent from acid and episodic streams have life cycles that would increase acid exposure risks during autumn and winter, and this may be sufficient to explain their current distribution.
Molecular characterization and evolution of the repeating units of histone genes in Drosophila americana: coexistence of quartet and quintet units in a genome
Authors: Nagoda N. , Fukuda A. , Nakashima Y. , Matsuo Y. 
Published: November 2005

AbstractQuintet and quartet repeating units of the histone genes in Drosophila americana were cloned and characterized. Nucleotide sequence analysis of the units showed that a 3175 bp unit contained the core histone genes but lacked the H1 gene (‘quartet unit’) while a 5025 bp unit contained all five histone genes (‘quintet unit’). Comparative analysis suggested that these repeating units diverged before the separation of D. americana and D. virilis. Multiple forms of H1 genes, differing by 5.8% of amino acids, were found in D. americana. The genomic organization of the histone gene family in D. americana was found to be very similar to that of D. virilis.
Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination
Authors: Hamilton Holly L. , Dillard Joseph P. 
Published: November 2005

SummaryGonococci undergo frequent and efficient natural transformation. Transformation occurs so often that the population structure is panmictic, with only one long‐lived clone having been identified. This high degree of genetic exchange is likely necessary to generate antigenic diversity and allow the persistence of gonococcal infection within the human population. In addition to spreading different alleles of genes for surface markers and allowing avoidance of the immune response, transformation facilitates the spread of antibiotic resistance markers, a continuing problem for treatment of gonococcal infections. Transforming DNA is donated by neighbouring gonococci by two different mechanisms: autolysis or type IV secretion. All types of DNA are bound non‐specifically to the cell surface. However, for DNA uptake, Neisseria gonorrhoeae recognizes only DNA containing a 10‐base sequence (GCCGTCTGAA) present frequently in the chromosome of neisserial species. Type IV pilus components and several pilus‐associated proteins are necessary for gonococcal DNA uptake. Incoming DNA is subject to restriction, making establishment of replicating plasmids difficult but not greatly affecting chromosomal transformation. Processing and integration of transforming DNA into the chromosome involves enzymes required for homologous recombination. Recent research on DNA donation mechanisms and extensive work on type IV pilus biogenesis and recombination proteins have greatly improved our understanding of natural transformation in N. gonorrhoeae. The completion of the gonococcal genome sequence has facilitated the identification of additional transformation genes and provides insight into previous investigations of gonococcal transformation. Here we review these recent developments and address the implications of natural transformation in the evolution and pathogenesis N. gonorrhoeae.
A phosphorelay system controls stalk biogenesis during cell cycle progression in Caulobacter crescentus
Authors: Biondi Emanuele G. , Skerker Jeffrey M. , Arif Muhammad , Prasol Melanie S. , Perchuk Barrett S. , Laub Michael T. 
Published: November 2005

SummaryA fundamental question in developmental biology is how morphogenesis is coordinated with cell cycle progression. In Caulobacter crescentus, each cell cycle produces morphologically distinct daughter cells, a stalked cell and a flagellated swarmer cell. Construction of both the flagellum and stalk requires the alternative sigma factor RpoN (σ54). Here we report that a σ54‐dependent activator, TacA, is required for cell cycle regulated stalk biogenesis by collaborating with RpoN to activate gene expression. We have also identified the first histidine phosphotransferase in C. crescentus, ShpA, and show that it too is required for stalk biogenesis. Using a systematic biochemical technique called phosphotransfer profiling we have identified a multicomponent phosphorelay which leads from the hybrid histidine kinase ShkA to ShpA and finally to TacA. This pathway functions in vivo to phosphorylate and hence, activate TacA. Finally, whole genome microarrays were used to identify candidate members of the TacA regulon, and we show that at least one target gene, staR, regulates stalk length. This is the first example of a general method for identifying the connectivity of a phosphorelay and can be applied to any organism with two‐component signal transduction systems.
Requirement of aminoacyl‐tRNA synthetases for gametogenesis and embryo development in Arabidopsis
Authors: Berg Michael , Rogers Rebecca , Muralla Rosanna , Meinke David 
Published: November 2005

SummaryAminoacyl‐tRNA synthetases (AARSs) are required for translation in three different compartments of the plant cell: chloroplasts, mitochondria and the cytosol. Elimination of this basal function should result in lethality early in development. Phenotypes of individual mutants may vary considerably, depending on patterns of gene expression, functional redundancy, allele strength and protein localization. We describe here a reverse genetic screen of 50 insertion mutants disrupted in 21 of the 45 predicted AARSs in Arabidopsis. Our initial goal was to find additional EMB genes with a loss‐of‐function phenotype in the seed. Several different classes of knockouts were discovered, with defects in both gametogenesis and seed development. Three major trends were observed. Disruption of translation in chloroplasts often results in seed abortion at the transition stage of embryogenesis with minimal effects on gametophytes. Disruption of translation in mitochondria often results in ovule abortion before and immediately after fertilization. This early phenotype was frequently missed in prior screens for embryo‐defective mutants. Knockout alleles of non‐redundant cytosolic AARSs were in general not identified, consistent with the absolute requirement of cytosolic translation for development of male and female gametophytes. These results provide a framework for evaluating redundant functions of AARSs in Arabidopsis, a valuable data set of phenotypes resulting from multiple disruptions of a single basal process, and insights into which genes are required for both gametogenesis and embryo development and might therefore escape detection in screens for embryo‐defective mutants.