bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung fibroblasts from patients with emphysema show markers of senescence in vitro
Authors: Müller K-C , Welker L , Paasch K , Feindt B , Erpenbeck VJ , Hohlfeld JM , Krug N , Nakashima M , Branscheid D , Magnussen H , Jörres RA , Holz O 
Published: February 2006

Abstract

Background
The loss of alveolar walls is a hallmark of emphysema. As fibroblasts play an important role in the maintenance of alveolar structure, a change in fibroblast phenotype could be involved in the pathogenesis of this disease. In a previous study we found a reduced in vitro proliferation rate and number of population doublings of parenchymal lung fibroblasts from patients with emphysema and we hypothesized that these findings could be related to a premature cellular aging of these cells. In this study, we therefore compared cellular senescence markers and expression of respective genes between lung fibroblasts from patients with emphysema and control patients without COPD.

Methods
Primary lung fibroblasts were obtained from 13 patients with moderate to severe lung emphysema (E) and 15 controls (C) undergoing surgery for lung tumor resection or volume reduction (n = 2). Fibroblasts (8E/9C) were stained for senescence-associated β-galactosidase (SA-β-Gal). In independent cultures, DNA from lung fibroblasts (7E/8C) was assessed for mean telomere length. Two exploratory 12 k cDNA microarrays were used to assess gene expression in pooled fibroblasts (3E/3C). Subsequently, expression of selected genes was evaluated by quantitative PCR (qPCR) in fibroblasts of individual patients (10E/9C) and protein concentration was analyzed in the cell culture supernatant.

Results
The median (quartiles) percentage of fibroblasts positive for SA-β-Gal was 4.4 (3.2;4.7) % in controls and 16.0 (10.0;24.8) % in emphysema (p = 0.001), while telomere length was not different. Among the candidates for differentially expressed genes in the array (factor ≥ 3), 15 were upregulated and 121 downregulated in emphysema. qPCR confirmed the upregulation of insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-rP1 (p = 0.029, p = 0.0002), while expression of IGFBP-5, -rP2 (CTGF), -rP4 (Cyr61), FOSL1, LOXL2, OAZ1 and CDK4 was not different between groups. In line with the gene expression we found increased cell culture supernatant concentrations of IGFBP-3 (p = 0.006) in emphysema.

Conclusion
These data support the hypothesis that premature aging of lung fibroblasts occurs in emphysema, via a telomere-independent mechanism. The upregulation of the senescence-associated IGFBP-3 and -rP1 in emphysema suggests that inhibition of the action of insulin and insulin-like growth factors could be involved in the reduced in vitro-proliferation rate.
Ca2+-signaling in airway smooth muscle cells is altered in T-bet knock-out mice
Authors: Bergner Albrecht , Kellner Julia , Kemp da Silva Anita , Gamarra Fernando , Huber Rudolf M 
Published: February 2006

Abstract

Background
Airway smooth muscle cells (ASMC) play a key role in bronchial hyperresponsiveness (BHR). A major component of the signaling cascade leading to ASMC contraction is calcium. So far, agonist-induced Ca2+-signaling in asthma has been studied by comparing innate properties of inbred rat or mouse strains, or by using selected mediators known to be involved in asthma. T-bet knock-out (KO) mice show key features of allergic asthma such as a shift towards TH2-lymphocytes and display a broad spectrum of asthma-like histological and functional characteristics. In this study, we aimed at investigating whether Ca2+-homeostasis of ASMC is altered in T-bet KO-mice as an experimental model of asthma.

Methods
Lung slices of 100 to 200 μm thickness were obtained from T-bet KO- and wild-type mice. Airway contraction in response to acetylcholine (ACH) was measured by video-microscopy and Ca2+-signaling in single ASMC of lung slices was assessed using two-photon-microscopy.

Results
Airways from T-bet KO-mice showed increased baseline airway tone (BAT) and BHR compared to wild-type mice. This could be mimicked by incubation of lung slices from wild-type mice with IL-13. The increased BAT was correlated with an increased incidence of spontaneous changes in intracellular Ca2+-concentrations, whereas BHR correlated with higher ACH-induced Ca2+-transients and an increased proportion of ASMC showing Ca2+-oscillations. Emptying intracellular Ca2+-stores using caffeine or cyclopiazonic acid induced higher Ca2+-elevations in ASMC from T-bet KO- compared to wild-type mice.

Conclusion
Altered Ca2+-homeostasis of ASMC contributes to increased BAT and BHR in lung slices from T-bet KO-mice as a murine asthma model. We propose that a higher Ca2+-content of the intracellular Ca2+-stores is involved in the pathophysiology of these changes.
Airway smooth muscle relaxation results from a reduction in the frequency of Ca2+ oscillations induced by a cAMP-mediated inhibition of the IP3 receptor
Authors: Bai Yan , Sanderson Michael J 
Published: February 2006

AbstractBackgroundIt has been shown that the contractile state of airway smooth muscle cells (SMCs) in response to agonists is determined by the frequency of Ca2+oscillations occurring within the SMCs. Therefore, we hypothesized that the relaxation of airway SMCs induced by agents that increase cAMP results from the down-regulation or slowing of the frequency of the Ca2+oscillations.MethodsThe effects of isoproterenol (ISO), forskolin (FSK) and 8-bromo-cAMP on the relaxation and Ca2+signaling of airway SMCs contracted with methacholine (MCh) was investigated in murine lung slices with phase-contrast and laser scanning microscopy.ResultsAll three cAMP-elevating agents simultaneously induced a reduction in the frequency of Ca2+oscillations within the SMCs and the relaxation of contracted airways. The decrease in the Ca2+oscillation frequency correlated with the extent of airway relaxation and was concentration-dependent. The mechanism by which cAMP reduced the frequency of the Ca2+oscillations was investigated. Elevated cAMP did not affect the re-filling rate of the internal Ca2+stores after emptying by repetitive exposure to 20 mM caffeine. Neither did elevated cAMP limit the Ca2+available to stimulate contraction because an elevation of intracellular Ca2+concentration induced by exposure to a Ca2+ionophore (ionomycin) or by photolysis of caged-Ca2+did not reverse the effect of cAMP. Similar results were obtained with iberiotoxin, a blocker of Ca2+-activated K+channels, which would be expected to increase Ca2+influx and contraction. By contrast, the photolysis of caged-IP3in the presence of agonist, to further elevate the intracellular IP3concentration, reversed the slowing of the frequency of the Ca2+oscillations and relaxation of the airway induced by FSK. This result implied that the sensitivity of the IP3R to IP3was reduced by FSK and this was supported by the reduced ability of IP3to release Ca2+in SMCs in the presence of FSK.ConclusionThese results indicate that the relaxant effect of cAMP-elevating agents on airway SMCs is achieved by decreasing the Ca2+oscillation frequency by reducing internal Ca2+release through IP3receptors.
BIPAD: A web server for modeling bipartite sequence elements
Authors: Bi Chengpeng , Rogan Peter K 
Published: February 2006

Abstract

Background
Many dimeric protein complexes bind cooperatively to families of bipartite nucleic acid sequence elements, which consist of pairs of conserved half-site sequences separated by intervening distances that vary among individual sites.

Results
We introduce the Bipad Server [1], a web interface to predict sequence elements embedded within unaligned sequences. Either a bipartite model, consisting of a pair of one-block position weight matrices (PWM's) with a gap distribution, or a single PWM matrix for contiguous single block motifs may be produced. The Bipad program performs multiple local alignment by entropy minimization and cyclic refinement using a stochastic greedy search strategy. The best models are refined by maximizing incremental information contents among a set of potential models with varying half site and gap lengths.

Conclusion
The web service generates information positional weight matrices, identifies binding site motifs, graphically represents the set of discovered elements as a sequence logo, and depicts the gap distribution as a histogram. Server performance was evaluated by generating a collection of bipartite models for distinct DNA binding proteins.
Taxonomic colouring of phylogenetic trees of protein sequences
Authors: Palidwor Gareth , Reynaud Emmanuel G , Andrade-Navarro Miguel A 
Published: February 2006

Abstract

Background
Phylogenetic analyses of protein families are used to define the evolutionary relationships between homologous proteins. The interpretation of protein-sequence phylogenetic trees requires the examination of the taxonomic properties of the species associated to those sequences. However, there is no online tool to facilitate this interpretation, for example, by automatically attaching taxonomic information to the nodes of a tree, or by interactively colouring the branches of a tree according to any combination of taxonomic divisions. This is especially problematic if the tree contains on the order of hundreds of sequences, which, given the accelerated increase in the size of the protein sequence databases, is a situation that is becoming common.

Results
We have developed PhyloView, a web based tool for colouring phylogenetic trees upon arbitrary taxonomic properties of the species represented in a protein sequence phylogenetic tree. Provided that the tree contains SwissProt, SpTrembl, or GenBank protein identifiers, the tool retrieves the taxonomic information from the corresponding database. A colour picker displays a summary of the findings and allows the user to associate colours to the leaves of the tree according to any number of taxonomic partitions. Then, the colours are propagated to the branches of the tree.

Conclusion
PhyloView can be used at http://www.ogic.ca/projects/phyloview/. A tutorial, the software with documentation, and GPL licensed source code, can be accessed at the same web address.
Gene annotation and network inference by phylogenetic profiling
Authors: Wu Jie , Hu Zhenjun , DeLisi Charles 
Published: February 2006

AbstractBackgroundPhylogenetic analysis is emerging as one of the most informative computational methods for the annotation of genes and identification of evolutionary modules of functionally related genes. The effectiveness with which phylogenetic profiles can be utilized to assign genes to pathways depends on an appropriate measure of correlation between gene profiles, and an effective decision rule to use the correlate. Current methods, though useful, perform at a level well below what is possible, largely because performance of the latter deteriorates rapidly as coverage increases.ResultsWe introduce, test and apply a new decision rule, correlation enrichment (CE), for assigning genes to functional categories at various levels of resolution. Among the results are: (1) CE performs better than standard guilt by association (SGA, assignment to a functional category when a simple correlate exceeds a pre-specified threshold) irrespective of the number of genes assigned (i.e.coverage); improvement is greatest at high coverage where precision (positive predictive value) of CE is approximately 6-fold higher than that of SGA. (2) CE is estimated to allocate each of the 2918 unannotated orthologs to KEGG pathways with an average precision of 49% (approximately 7-fold higher than SGA) (3) An estimated 94% of the 1846 unannotated orthologs in the COG ontology can be assigned a function with an average precision of 0.4 or greater. (4) Dozens of functional and evolutionarily conserved cliques or quasi-cliques can be identified, many having previously unannotated genes.ConclusionThe method serves as a general computational tool for annotating large numbers of unknown genes, uncovering evolutionary and functional modules. It appears to perform substantially better than extant stand alone high throughout methods.
PhosphoregDB: The tissue and sub-cellular distribution of mammalian protein kinases and phosphatases
Authors: Forrest Alistair RR , Taylor Darrin F , Fink J Lynn , Gongora M Milena , Flegg Cameron , Teasdale Rohan D , Suzuki Harukazu , Kanamori Mutsumi , Kai Chikatoshi , Hayashizaki Yoshihide , Grimmond Sean M 
Published: February 2006

Abstract

Background
Protein kinases and protein phosphatases are the fundamental components of phosphorylation dependent protein regulatory systems. We have created a database for the protein kinase-like and phosphatase-like loci of mouse http://phosphoreg.imb.uq.edu.au that integrates protein sequence, interaction, classification and pathway information with the results of a systematic screen of their sub-cellular localization and tissue specific expression data mined from the GNF tissue atlas of mouse.

Results
The database lets users query where a specific kinase or phosphatase is expressed at both the tissue and sub-cellular levels. Similarly the interface allows the user to query by tissue, pathway or sub-cellular localization, to reveal which components are co-expressed or co-localized. A review of their expression reveals 30% of these components are detected in all tissues tested while 70% show some level of tissue restriction. Hierarchical clustering of the expression data reveals that expression of these genes can be used to separate the samples into tissues of related lineage, including 3 larger clusters of nervous tissue, developing embryo and cells of the immune system. By overlaying the expression, sub-cellular localization and classification data we examine correlations between class, specificity and tissue restriction and show that tyrosine kinases are more generally expressed in fewer tissues than serine/threonine kinases.

Conclusion
Together these data demonstrate that cell type specific systems exist to regulate protein phosphorylation and that for accurate modelling and for determination of enzyme substrate relationships the co-location of components needs to be considered.
CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays
Authors: Huang Jing , Wei Wen , Chen Joyce , Zhang Jane , Liu Guoying , Di Xiaojun , Mei Rui , Ishikawa Shumpei , Aburatani Hiroyuki , Jones Keith W , Shapero Michael H 
Published: February 2006

AbstractBackgroundDNA copy number alterations are one of the main characteristics of the cancer cell karyotype and can contribute to the complex phenotype of these cells. These alterations can lead to gains in cellular oncogenes as well as losses in tumor suppressor genes and can span small intervals as well as involve entire chromosomes. The ability to accurately detect these changes is central to understanding how they impact the biology of the cell.ResultsWe describe a novel algorithm called CARAT (Copy NumberAnalysis withRegressionAndTree) that uses probe intensity information to infer copy number in an allele-specific manner from high density DNA oligonuceotide arrays designed to genotype over 100, 000 SNPs. Total and allele-specific copy number estimations using CARAT are independently evaluated for a subset of SNPs using quantitative PCR and allelic TaqMan reactions with several human breast cancer cell lines. The sensitivity and specificity of the algorithm are characterized using DNA samples containing differing numbers of X chromosomes as well as a test set of normal individuals. Results from the algorithm show a high degree of agreement with results from independent verification methods.ConclusionOverall, CARAT automatically detects regions with copy number variations and assigns a significance score to each alteration as well as generating allele-specific output. When coupled with SNP genotype calls from the same array, CARAT provides additional detail into the structure of genome wide alterations that can contribute to allelic imbalance.
Statistical analysis of real-time PCR data
Authors: Yuan Joshua S , Reed Ann , Chen Feng , Stewart C Neal 
Published: February 2006

Abstract

Background
Even though real-time PCR has been broadly applied in biomedical sciences, data processing procedures for the analysis of quantitative real-time PCR are still lacking; specifically in the realm of appropriate statistical treatment. Confidence interval and statistical significance considerations are not explicit in many of the current data analysis approaches. Based on the standard curve method and other useful data analysis methods, we present and compare four statistical approaches and models for the analysis of real-time PCR data.

Results
In the first approach, a multiple regression analysis model was developed to derive ΔΔCt from estimation of interaction of gene and treatment effects. In the second approach, an ANCOVA (analysis of covariance) model was proposed, and the ΔΔCt can be derived from analysis of effects of variables. The other two models involve calculation ΔCt followed by a two group t- test and non-parametric analogous Wilcoxon test. SAS programs were developed for all four models and data output for analysis of a sample set are presented. In addition, a data quality control model was developed and implemented using SAS.

Conclusion
Practical statistical solutions with SAS programs were developed for real-time PCR data and a sample dataset was analyzed with the SAS programs. The analysis using the various models and programs yielded similar results. Data quality control and analysis procedures presented here provide statistical elements for the estimation of the relative expression of genes using real-time PCR.
BayGO: Bayesian analysis of ontology term enrichment in microarray data
Authors: Vêncio Ricardo ZN , Koide Tie , Gomes Suely L , de B Pereira Carlos A 
Published: February 2006

Abstract

Background
The search for enriched (aka over-represented or enhanced) ontology terms in a list of genes obtained from microarray experiments is becoming a standard procedure for a system-level analysis. This procedure tries to summarize the information focussing on classification designs such as Gene Ontology, KEGG pathways, and so on, instead of focussing on individual genes. Although it is well known in statistics that association and significance are distinct concepts, only the former approach has been used to deal with the ontology term enrichment problem.

Results
BayGO implements a Bayesian approach to search for enriched terms from microarray data. The R source-code is freely available at http://blasto.iq.usp.br/~tkoide/BayGO in three versions: Linux, which can be easily incorporated into pre-existent pipelines; Windows, to be controlled interactively; and as a web-tool. The software was validated using a bacterial heat shock response dataset, since this stress triggers known system-level responses.

Conclusion
The Bayesian model accounts for the fact that, eventually, not all the genes from a given category are observable in microarray data due to low intensity signal, quality filters, genes that were not spotted and so on. Moreover, BayGO allows one to measure the statistical association between generic ontology terms and differential expression, instead of working only with the common significance analysis.
SIMMAP: Stochastic character mapping of discrete traits on phylogenies
Authors: Bollback Jonathan P 
Published: February 2006

AbstractBackgroundCharacter mapping on phylogenies has played an important, if not critical role, in our understanding of molecular, morphological, and behavioral evolution. Until very recently we have relied on parsimony to infer character changes. Parsimony has a number of serious limitations that are drawbacks to our understanding. Recent statistical methods have been developed that free us from these limitations enabling us to overcome the problems of parsimony by accommodating uncertainty in evolutionary time, ancestral states, and the phylogeny.ResultsSIMMAP has been developed to implement stochastic character mapping that is useful to both molecular evolutionists, systematists, and bioinformaticians. Researchers can address questions about positive selection, patterns of amino acid substitution, character association, and patterns of morphological evolution.ConclusionStochastic character mapping, as implemented in the SIMMAP software, enables users to address questions that require mapping characters onto phylogenies using a probabilistic approach that does not rely on parsimony. Analyses can be performed using a fully Bayesian approach that is not reliant on considering a single topology, set of substitution model parameters, or reconstruction of ancestral states. Uncertainty in these quantities is accommodated by using MCMC samples from their respective posterior distributions.
Interleukin-1α enhances the aggressive behavior of pancreatic cancer cells by regulating the α6β1-integrin and urokinase plasminogen activator receptor expression
Authors: Sawai Hirozumi , Okada Yuji , Funahashi Hitoshi , Matsuo Yoichi , Takahashi Hiroki , Takeyama Hiromitsu , Manabe Tadao 
Published: February 2006

Abstract

Background
In human pancreatic cancer progression, the α6β1-integrin is expressed on cancer cell surface during invasion and metastasis formation. In this study, we investigated whether interleukin (IL)-1α induces the alterations of integrin subunits and urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) expression in pancreatic cancer cells. We hypothesize that the alterations of integrin subunits and uPA/uPAR expression make an important role in signaling pathways responsible for biological behavior of pancreatic cancer cells.

Results
IL-1α upregulated the expression of α6 and β1 integrins without any alterations of α5 and αv integrins expression. IL-1α also induced enhancement in the expression of uPA/uPAR in pancreatic cancer cells. IL-1α enhanced the proliferation, adhesion, and migration in pancreatic cancer cells, and IL-1α-induced alterations of uPA/uPAR expression correlated with the increased the migration of pancreatic cancer cells. Upregulation of α6 integrin subunit and uPA/uPAR correlated with the activation of Ras and downstream extracellular signal-regulated kinase (ERK) pathways. IL-1α-induced activation of Ras and downstream ERK can be inhibited by using inhibitory antibodies against α6 and β1 integrin and uPAR, consistent with the inhibition of proliferation, adhesion and migration of pancreatic cancer cells. Immunohistochemical analysis demonstrated a significant association between strong expressions of α6 integrin with uPAR in pancreatic cancer specimens. Furthermore, the strong expression of α6 integrin and uPAR was found to be independent prognosticator in pancreatic cancer patients.

Conclusion
Based on these findings, we conclude that IL-1α can induce selective upregulation of α6β1-integrin and uPA/uPAR in pancreatic cancer cells and these changes may modulate the aggressive functions of pancreatic cancer.