bluuebunny/crossref_metadata_2025 huggingface dataset:
GoArrays: highly dynamic and efficient microarray probe design
Authors: Rimour Sébastien , Hill David , Militon Cécile , Peyret Pierre
Published: November 2004

Motivation: The use of oligonucleotide microarray technology requires a very detailed attention to the design of specific probes spotted on the solid phase. These problems are far from being commonplace since they refer to complex physicochemical constraints. Whereas there are more and more publicly available programs for microarray oligonucleotide design, most of them use the same algorithm or criteria to design oligos, with only little variation.

Results: We show that classical approaches used in oligo design software may be inefficient under certain experimental conditions, especially when dealing with complex target mixtures. Indeed, our biological model is a human obligate parasite, the microsporidia Encephalitozoon cuniculi. Targets that are extracted from biological samples are composed of a mixture of pathogen transcripts and host cell transcripts. We propose a new approach to design oligonucleotides which combines good specificity with a potentially high sensitivity. This approach is original in the biological point of view as well as in the algorithmic point of view. We also present an experimental validation of this new strategy by comparing results obtained with standard oligos and with our composite oligos. A specific E.cuniculi microarray will overcome the difficulty to discriminate the parasite mRNAs from the host cell mRNAs demonstrating the power of the microarray approach to elucidate the lifestyle of an intracellular pathogen using mix mRNAs.

Availability: Our method is implemented in the GoArrays software, available at http://www.isima.fr/bioinfo/goarrays/

Contact: rimour@isima.fr for computing part, and pierre.peyret@univ-bpclermont.fr for collaborative projects.
Extracting multiple structural alignments from pairwise alignments: a comparison of a rigorous and a heuristic approach
Authors: Sandelin Erik
Published: November 2004

Motivation: Multiple structural alignments (MSTAs) provide position-specific information on the sequence variability allowed by protein folds. This information can be exploited to better understand the evolution of proteins and the physical chemistry of polypeptide folding. Most MSTA methods rely on a pre-computed library of pairwise alignments. This library will in general contain conflicting residue equivalences not all of which can be realized in the final MSTA. Hence to build a consistent MSTA, these methods have to select a conflict-free subset of equivalences.

Results: Using a dataset with 327 families from SCOP 1.63 we compare the ability of two different methods to select an optimal conflict-free subset of equivalences. One is an implementation of Reinert et al.'s integer linear programming formulation (ILP) of the maximum weight trace problem (Reinert et al., 1997, Proc. 1st Ann. Int. Conf. Comput. Mol. Biol. (RECOMB-97), ACM Press, New York). This ILP formulation is a rigorous approach but its complexity is difficult to predict. The other method is T-Coffee (Notredame et al., 2000) which uses a heuristic enhancement of the equivalence weights which allow it to use the speed and simplicity of the progressive alignment approach while still incorporating information of all alignments in each step of building the MSTA. We find that although the ILP formulation consistently selects a more optimal set of conflict-free equivalences, the differences are small and the quality of the resulting MSTAs are essentially the same for both methods. Given its speed and predictable complexity, our results show that T-Coffee is an attractive alternative for producing high-quality MSTAs.

Availability: The software for Resolver, our implementation of Reinert et al.'s ILP formulation, and the dataset used in this study are available at http://www.sbc.su.se/~erik/resolver

Contact:  erik@sbc.su.se
Sensitivity, principal component and flux analysis applied to signal transduction: the case of epidermal growth factor mediated signaling
Authors: Liu Gang , Swihart Mark T. , Neelamegham Sriram
Published: November 2004

Motivation: Novel high-throughput genomic and proteomic tools are allowing the integration of information from a range of biological assays into a single conceptual framework. This framework is often described as a network of biochemical reactions. We present strategies for the analysis of such networks.

Results: The direct differential method is described for the systematic evaluation of scaled sensitivity coefficients in reaction networks. Principal component analysis, based on an eigenvalue–eigenvector analysis of the scaled sensitivity coefficient matrix, is applied to rank individual reactions in the network based on their effect on system output. When combined with flux analysis, sensitivity analysis allows model reduction or simplification. Using epidermal growth factor (EGF) mediated signaling and trafficking as an example of signal transduction, we demonstrate that sensitivity analysis quantitatively reveals the dependence of dual-phosphorylated extracellular signal-regulated kinase (ERK) concentration on individual reaction rate constants. It predicts that EGF mediated reactions proceed primarily via an Shc-dependent pathway. Further, it suggests that receptor internalization and endosomal signaling are important features regulating signal output only at low EGF dosages and at later times.

Contact:  neel@eng.buffalo.edu

Supplemental data:  http://www.eng.buffalo.edu/~neel/bio_reaction_network.html
OMGProm: a database of orthologous mammalian gene promoters
Authors: Palaniswamy Saranyan K. , Jin Victor X. , Sun Hao , Davuluri Ramana V.
Published: November 2004

Summary: Sequence comparisons between human and rodents are increasingly being used for the identification of gene regulatory regions. The effectiveness of such an approach largely depends on the quality and availability of promoter sequences. We developed OMGProm by integrating three data sources: (1) experimentally supported full-length cDNA, promoter and first exon sequences; (2) homology information from HomoloGene and (3) the human and mouse genomic sequences. The current version of OMGProm contains 8550 promoter pairs of 6373 orthologous human and mouse genes, where supporting experimental evidence for transcription start site annotation exists in at least one species.

Availability: OMGProm can be accessed from http://bioinformatics.med.ohio-state.edu/OMGProm

Contact:  davuluri-1@medctr.osu.edu

Supplementary information: Additional information on methods and implementation is available at http://bioinformatics.med.ohio-state.edu/OMGProm/si.jsp.
A Java tool for dynamic web-based 3D visualization of anatomy and overlapping gene or protein expression patterns
Authors: Gerth Victor E. , Vize Peter D.
Published: November 2004

Summary: The Gene Expression Viewer is a web-launched three-dimensional visualization tool, tailored to compare surface reconstructions of multi-channel image volumes generated by confocal microscopy or micro-CT.

Availability: Software is available on request from the authors and is free to academics.

Contact:  pvize@ucalgary.ca

Supplementary information: Revisions and additional documentation to the Gene Expression Viewer are maintained at http://www.cbrbio.ucalgary.ca/3DModels and http://www.xenbase.org/3DModels. The idx3dIII Advanced Programming Interface is freely available for non-commercial use at http://www.idx3d.ch/
Protein homology detection by HMM–HMM comparison
Authors: Söding Johannes
Published: November 2004

Motivation: Protein homology detection and sequence alignment are at the basis of protein structure prediction, function prediction and evolution.

Results: We have generalized the alignment of protein sequences with a profile hidden Markov model (HMM) to the case of pairwise alignment of profile HMMs. We present a method for detecting distant homologous relationships between proteins based on this approach. The method (HHsearch) is benchmarked together with BLAST, PSI-BLAST, HMMER and the profile–profile comparison tools PROF_SIM and COMPASS, in an all-against-all comparison of a database of 3691 protein domains from SCOP 1.63 with pairwise sequence identities below 20%.

Sensitivity: When the predicted secondary structure is included in the HMMs, HHsearch is able to detect between 2.7 and 4.2 times more homologs than PSI-BLAST or HMMER and between 1.44 and 1.9 times more than COMPASS or PROF_SIM for a rate of false positives of 10%. Approximately half of the improvement over the profile–profile comparison methods is attributable to the use of profile HMMs in place of simple profiles.

Alignment quality: Higher sensitivity is mirrored by an increased alignment quality. HHsearch produced 1.2, 1.7 and 3.3 times more good alignments (‘balanced’ score >0.3) than the next best method (COMPASS), and 1.6, 2.9 and 9.4 times more than PSI-BLAST, at the family, superfamily and fold level, respectively.

Speed: HHsearch scans a query of 200 residues against 3691 domains in 33 s on an AMD64 2GHz PC. This is 10 times faster than PROF_SIM and 17 times faster than COMPASS.

Availability: HHsearch can be downloaded from http://www.protevo.eb.tuebingen.mpg.de/download/ together with up-to-date versions of SCOP and PFAM. A web server is available at http://www.protevo.eb.tuebingen.mpg.de/toolkit/index.php?view=hhpred

Contact:  johannes.soeding@tuebingen.mpg.de
A simple statistical method for discriminating outer membrane proteins with better accuracy
Authors: Gromiha M. Michael , Suwa Makiko
Published: November 2004

Motivation: Discriminating outer membrane proteins from other folding types of globular and membrane proteins is an important task both for identifying outer membrane proteins from genomic sequences and for the successful prediction of their secondary and tertiary structures.

Results: We have systematically analyzed the amino acid composition of globular proteins from different structural classes and outer membrane proteins. We found that the residues, Glu, His, Ile, Cys, Gln, Asn and Ser, show a significant difference between globular and outer membrane proteins. Based on this information, we have devised a statistical method for discriminating outer membrane proteins from other globular and membrane proteins. Our approach correctly picked up the outer membrane proteins with an accuracy of 89% for the training set of 337 proteins. On the other hand, our method has correctly excluded the globular proteins at an accuracy of 79% in a non-redundant dataset of 674 proteins. Furthermore, the present method is able to correctly exclude α-helical membrane proteins up to an accuracy of 80%. These accuracy levels are comparable to other methods in the literature, and this is a simple method, which could be used for dissecting outer membrane proteins from genomic sequences. The influence of protein size, structural class and specific residues for discrimination is discussed.

Availability: A program for the discrimination method is available upon request from the corresponding author. The datasets used in this work are available at http://www.cbrc.jp/~gromiha/omp/dataset.html

Contact:  michael-gromiha@aist.go.jp
Non-sequential structure-based alignments reveal topology-independent core packing arrangements in proteins
Authors: Yuan Xin , Bystroff Christopher
Published: November 2004

Motivation: Proteins of the same class often share a secondary structure packing arrangement but differ in how the secondary structure units are ordered in the sequence. We find that proteins that share a common core also share local sequence–structure similarities, and these can be exploited to align structures with different topologies. In this study, segments from a library of local sequence–structure alignments were assembled hierarchically, enforcing the compactness and conserved inter-residue contacts but not sequential ordering. Previous structure-based alignment methods often ignore sequence similarity, local structural equivalence and compactness.

Results: The new program, SCALI (Structural Core ALIgnment), can efficiently find conserved packing arrangements, even if they are non-sequentially ordered in space. SCALI alignments conserve remote sequence similarity and contain fewer alignment errors. Clustering of our pairwise non-sequential alignments shows that recurrent packing arrangements exist in topologically different structures. For example, the three-layer sandwich domain architecture may be divided into four structural subclasses based on internal packing arrangements. These subclasses represent an intermediate level of structure classification, more general than topology, but more specific than architecture as defined in CATH. A strategy is presented for developing a set of predictive hidden Markov models based on multiple SCALI alignments.

Availability: An online topology-independent SCALI structure comparison server is available at http://www.bioinfo.rpi.edu/~bystrc/scali.html

Contact:  bystrc@rpi.edu
The promise and perils of exhaled breath condensates
Authors: Effros Richard M. , Dunning Marshall B. , Biller Julie , Shaker Reza
Published: November 2004

The exhaled breath condensate (EBC) approach provides a convenient and noninvasive approach for sampling the pulmonary epithelial lining fluid (ELF). Increased EBC concentrations of more than a dozen inflammatory markers and hydrogen ions have been reported in lung diseases associated with inflammation. However, the usefulness of EBC is compromised by uncertainties concerning the sources of the EBC droplets and by the extreme and variable dilution of ELF droplets with condensed water vapor (∼20,000-fold). Reported increases in EBC concentrations may reflect proportionate increases in the total volume rather than the concentration of ELF droplets in the collected samples. Conclusions regarding ELF concentrations can only be made if this dilution is estimated with a dilutional indicator (e.g., conductivity of lyophilized EBC). In normal EBC samples, pH is effectively set by oral contamination with NH3, and EBC pH cannot provide reliable information regarding ELF pH in normal subjects. Acidification of EBC observed in asthma and other conditions may reflect acidification of ELF, decreases in NH3 added to the EBC, and/or the presence of gastric droplets in the EBC.
Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries
Authors: Woodman Christopher R. , Price Elmer M. , Laughlin M. Harold
Published: November 2004

We tested the hypothesis that increased intraluminal shear stress induces endothelial nitric oxide (NO) synthase (eNOS) mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries (SFA) by increasing NO production. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two resistance-matched glass micropipettes. SFA were exposed to no flow (NF), low flow (LF), intermediate flow (IF), or high flow (HF) for 4 h. Mean intraluminal shear stress ranged from 0 to 82 dyn/cm2. At the end of the 4-h treatment period, eNOS mRNA expression was assessed in each SFA. eNOS mRNA expression was significantly lower in old NF SFA than in young NF SFA. In old SFA, eNOS mRNA expression was induced by IF (+154%) and HF (+136%), resulting in a level of expression that was not different from that of young SFA. In a separate series of experiments, SFA were pretreated with NF or HF for 4 h, and endothelial function was assessed by examining vasodilator responses to ACh. ACh-induced dilation was less in old NF SFA than young NF SFA. Pretreatment with HF improved ACh-induced dilation in old SFA such that the response was similar to that of young SFA. In the presence of Nω-nitro-l-arginine to inhibit NOS, ACh-induced dilation was inhibited in old HF SFA such that the response was no longer greater than that of old NF SFA. These results indicate that increased intraluminal shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent SFA by increasing NO production.
Endurance exercise training increases insulin responsiveness in isolated adipocytes through IRS/PI3-kinase/Akt pathway
Authors: Peres Sidney B. , de Moraes Solange M. Franzói , Costa Cecilia E. M. , Brito Luciana C. , Takada Julie , Andreotti Sandra , Machado Magaly A. , Alonso-Vale Maria Isabel C. , Borges-Silva Cristina N. , Lima Fabio B.
Published: November 2004

Endurance exercise training promotes important metabolic adaptations, and the adipose tissue is particularly affected. The aim of this study was to investigate how endurance exercise training modulates some aspects of insulin action in isolated adipocytes and in intact adipose tissue. Male Wistar rats were submitted to daily treadmill running (1 h/day) for 7 wk. Sedentary age-matched rats were used as controls. Final body weight, body weight gain, and epididymal fat pad weight did not show any statistical differences between groups. Adipocytes from trained rats were smaller than those from sedentary rats (205 ± 16.8 vs. 286 ± 26.4 pl; P < 0.05). Trained rats showed decreased plasma glucose (4.9 ± 0.13 vs. 5.3 ± 0.07 mM; P < 0.05) and insulin levels (0.24 ± 0.012 vs. 0.41 ± 0.049 mM; P < 0.05) and increased insulin-stimulated glucose uptake (23.1 ± 3.1 vs. 12.1 ± 2.9 pmol/cm2; P < 0.05) compared with sedentary rats. The number of insulin receptors and the insulin-induced tyrosine phosphorylation of insulin receptor-β subunit did not change between groups. Insulin-induced tyrosine phosphorylation insulin receptor substrates (IRS)-1 and -2 increased significantly (1.57- and 2.38-fold, respectively) in trained rats. Insulin-induced IRS-1/phosphatidylinositol 3 (PI3)-kinase (but not IRS-2/PI3-kinase) association and serine Akt phosphorylation also increased (2.06- and 3.15-fold, respectively) after training. The protein content of insulin receptor-β subunit, IRS-1 and -2, did not differ between groups. Taken together, these data support the hypothesis that the increased adipocyte responsiveness to insulin observed after endurance exercise training is modulated by IRS/PI3-kinase/Akt pathway.
Nonsymmetrical double logistic analysis of ambulatory blood pressure recordings
Authors: Head Geoffrey A. , Reid Christopher M. , Lukoshkova Elena V.
Published: November 2004

We developed an asymmetric double logistic curve-fitting procedure for circadian analysis that can determine the rate of change in variables during the day-to-night separately from the night-to-day transition for use in animal studies. We now have applied this procedure to 24-h systolic (SAP) and diastolic arterial pressure (DAP) and heart rate ambulatory recordings from 302 patients. In 292 cases, all parameters showed a pattern of higher day and lower night values. In men there was a similar rate of transition between day and night or from night to day for both SAP and DAP that lasted 3–4 h, indicating a symmetrical diurnal pattern. By contrast, women showed a faster rate of decrease in mean arterial pressure in the evening compared with men ( P < 0.05) and therefore showed an asymmetric diurnal SAP pattern. For both men and women, there was a markedly greater rate of morning increase in heart rate compared with the rate of evening decrease (2.2- and 1.9-fold, respectively, P < 0.001). The logistic method provided a better fit than the square-wave or the cosinor method ( P < 0.001) and more appropriately detected nondippers. We conclude that analysis of ambulatory recordings by a new logistic curve-fitting method reveals more rapid reductions in evening SAP in women than men but both have two- to threefold more rapid morning rates of tachycardia. The ability of the double logistic method to determine the diurnal blood pressure rates of change independently is key to determining new markers for cardiovascular risk.
Cardiovagal regulation during combined hypoxic and orthostatic stress: fainters vs. nonfainters
Authors: Halliwill John R. , Minson Christopher T.
Published: November 2004

We tested the hypothesis that individual differences in the effect of acute hypoxia on the cardiovagal arterial baroreflex would determine individual susceptibility to hypoxic syncope. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20–33 yr), we assessed orthostatic tolerance with a 20-min 60° head-upright tilt during both normoxia and hypoxia (breathing 12% O2). On a separate occasion, we assessed baroreflex control of heart rate (cardiovagal baroreflex gain) using the modified Oxford technique during both normoxia and hypoxia. When subjects were tilted under hypoxic conditions, 5 of the 16 developed presyncopal signs or symptoms, and the 20-min tilt had to be terminated. These “fainters” had comparable cardiovagal baroreflex gain to “nonfainters” under both normoxic and hypoxic conditions (normoxia, fainters: −1.2 ± 0.2, nonfainters: −1.0 ± 0.2 beats·min−1·mmHg−1, P = 0.252; hypoxia, fainters: −1.3 ± 0.2, nonfainters: −1.0 ± 0.1 beats·min−1·mmHg−1, P = 0.208). Furthermore, hypoxia did not alter cardiovagal baroreflex gain in either group (both P > 0.8). It appears from these observations that hypoxic syncope results from the superimposed vasodilator effects of hypoxia on the cardiovascular system and not from a hypoxia-induced maladjustment in baroreflex control of heart rate.
Once More . . . for the First Time: Aristotle and Hegel in the Logic of History
Authors: Warnek Peter
Published: November 2004

The paper begins by taking seriously Heidegger's provocative claims concerning Hegel's relationship to the Greeks. Most notably, the enigmatic assertion that Hegel, as the "last Greek," brings Greek philosophy to its completion through a historical thinking is considered in terms of the strange sense of repetition it opens up: the Hegelian presentation of Greek philosophy must both present that philosophy, repeat its movement, but also, in the repetition, present the truth of that movement for the first time. It thus must remain undecided whether Hegel's presentation only opens up a necessity already at work in Greek philosophical history or whether that presentation, in fact, first grants such necessity to that history. The singularity of Hegel's relation to the Greeks is then explored through an examination of Hegel's own statements concerning the singularity of Aristotle. In this way, it becomes apparent that Hegel's own thought, in its entirety, asserts itself as nothing other that a decisive repetition of the Aristotelian speculative thought of actuality. This exceptional position of Aristotle in Hegel's logic of history suggests that there is a need for another sense of history's movement, in which that movement does not simply progress but unfolds as the sin- gular dialogue between one Greek and one German.
Husserl's Theory of the Phenomenological Reduction: Between Life-world and Cartesianism
Authors: Luft Sebastian
Published: November 2004

This essay attempts a renewed, critical exposition of Husserl's theory of the phenomenological reduction, incorporating manuscript material that has been published since the defining essays of the first generation of Husserl research. The discussion focuses on points that

remain

especially crucial, i.e., the concept of the natural attitude, the ways into the reduction (and their systematics), and finally the question of the "meaning of the reduction." Indeed, in the reading attempted here, this final question leads to two, not necessarily related, focal points: a Cartesian and a Life-world tendency. It is my claim that in following these two paths, Husserl was consistent in pursuing two evident leads in his philosophical enterprise; however, he was at the same time unable to systematically unify these two strands. Thus, I am offering an interpretation which might be called a modified "departure from Cartesianism" reading that Landgrebe proposed in his famous essay from the 1950s, in which he was clearly influenced by Heidegger (a reading that is still valid in many contemporary expositions of Husserl's thought). This discussion should make apparent that Husserl's theory of the phenomenological reduction deserves a renewed look both in light of material that has since appeared in the

Husserliana

and in light of a new incorporation of the most important results of recent tendencies in Husserl research.
Establishing Trust via Technology: Long Distance Practices and Pitfalls
Authors: Naquin Charles , Paulson Gaylen
Published: November 2004

Global negotiators often depend upon communication technologies to convey information and strike deals. Unfortunately, negotiations conducted via more "lean" media (e.g., e-mail, telephone) have been associated with low levels of trust and difficulties in reaching agreements. We explore two approaches to building trust while communicating via the internet. Derived from the literature on interpersonal trust, negotiators were asked to adopt one of two strategies. The first was to build personal rapport. The second was to discuss ground rules and procedures for the negotiation. Negotiators who spent time building rapport reported greater levels of trust, and were more confident and satisfied with their outcomes. These perceptions were evident even though outcomes were comparable across conditions. The most negatively perceived negotiations were those that included rules discussions without the benefit of rapport. Implications of these findings for theory and practice are discussed.
d-matrix – database exploration, visualization and analysis
Authors: Seelow Dominik , Galli Raffaello , Mebus Siegrun , Sperling Hans-Peter , Lehrach Hans , Sperling Silke
Published: November 2004

Background

Motivated by a biomedical database set up by our group, we aimed to develop a generic database front-end with embedded knowledge discovery and analysis features. A major focus was the human-oriented representation of the data and the enabling of a closed circle of data query, exploration, visualization and analysis.

Results

We introduce a non-task-specific database front-end with a new visualization strategy and built-in analysis features, so called d-matrix. d-matrix is web-based and compatible with a broad range of database management systems. The graphical outcome consists of boxes whose colors show the quality of the underlying information and, as the name suggests, they are arranged in matrices. The granularity of the data display allows consequent drill-down. Furthermore, d-matrix offers context-sensitive categorization, hierarchical sorting and statistical analysis.

Conclusions

d-matrix enables data mining, with a high level of interactivity between humans and computer as a primary factor. We believe that the presented strategy can be very effective in general and especially useful for the integration of distinct data types such as phenotypical and molecular data.
Incremental genetic K-means algorithm and its application in gene expression data analysis
Authors: Lu Yi , Lu Shiyong , Fotouhi Farshad , Deng Youping , Brown Susan J
Published: November 2004

Background

In recent years, clustering algorithms have been effectively applied in molecular biology for gene expression data analysis. With the help of clustering algorithms such as K-means, hierarchical clustering, SOM, etc, genes are partitioned into groups based on the similarity between their expression profiles. In this way, functionally related genes are identified. As the amount of laboratory data in molecular biology grows exponentially each year due to advanced technologies such as Microarray, new efficient and effective methods for clustering must be developed to process this growing amount of biological data.

Results

In this paper, we propose a new clustering algorithm, Incremental Genetic K-means Algorithm (IGKA). IGKA is an extension to our previously proposed clustering algorithm, the Fast Genetic K-means Algorithm (FGKA). IGKA outperforms FGKA when the mutation probability is small. The main idea of IGKA is to calculate the objective value Total Within-Cluster Variation (TWCV) and to cluster centroids incrementally whenever the mutation probability is small. IGKA inherits the salient feature of FGKA of always converging to the global optimum. C program is freely available at http://database.cs.wayne.edu/proj/FGKA/index.htm.

Conclusions

Our experiments indicate that, while the IGKA algorithm has a convergence pattern similar to FGKA, it has a better time performance when the mutation probability decreases to some point. Finally, we used IGKA to cluster a yeast dataset and found that it increased the enrichment of genes of similar function within the cluster.
The Molecular Pages of the mesotelencephalic dopamine consortium (DopaNet)
Authors: Le Novère Nicolas , Donizelli Marco
Published: November 2004

Background

DopaNet http://www.dopanet.org is a Systems Biology initiative that aims to investigate precisely and quantitatively all the aspects of neurotransmission in a specific neuronal system, the mesotelencephalic dopamine system. The project should lead to large-scale models of molecular and cellular processes involved in neuronal signaling. A prerequisite is the proper storage of knowledge coming from the literature.

Methods

DopaNet Molecular Pages are highly structured descriptions of quantitative parameters related to a specific molecular complex involved in neuronal signal processing. A Molecular Page is built by maintainers who are experts in the field, and responsible for the quality of the page content. Each piece of data is identified by a specific ontology code, annotated (method of acquisition, species, etc.) and linked to the relevant bibliography. The Molecular Pages are stored as XML files, and processed through the DopaNet Web Service, which provides functionalities to edit the Molecular Pages, to cross-link the Pages and generate the public display, and to search them.

Conclusions

DopaNet Molecular Pages are one of the core resources of the DopaNet project but should be of widespread utility in the field of Systems Neurobiology.
An enigmatic fourth runt domain gene in the fugu genome: ancestral gene loss versus accelerated evolution
Authors: Glusman Gustavo , Kaur Amardeep , Hood Leroy , Rowen Lee
Published: November 2004

Background

The runt domain transcription factors are key regulators of developmental processes in bilaterians, involved both in cell proliferation and differentiation, and their disruption usually leads to disease. Three runt domain genes have been described in each vertebrate genome (the RUNX gene family), but only one in other chordates. Therefore, the common ancestor of vertebrates has been thought to have had a single runt domain gene.

Results

Analysis of the genome draft of the fugu pufferfish (Takifugu rubripes) reveals the existence of a fourth runt domain gene, FrRUNT, in addition to the orthologs of human RUNX1, RUNX2 and RUNX3. The tiny FrRUNT packs six exons and two putative promoters in just 3 kb of genomic sequence. The first exon is located within an intron of FrSUPT3H, the ortholog of human SUPT3H, and the first exon of FrSUPT3H resides within the first intron of FrRUNT. The two gene structures are therefore "interlocked". In the human genome, SUPT3H is instead interlocked with RUNX2. FrRUNT has no detectable ortholog in the genomes of mammals, birds or amphibians. We consider alternative explanations for an apparent contradiction between the phylogenetic data and the comparison of the genomic neighborhoods of human and fugu runt domain genes. We hypothesize that an ancient RUNT locus was lost in the tetrapod lineage, together with FrFSTL6, a member of a novel family of follistatin-like genes.

Conclusions

Our results suggest that the runt domain family may have started expanding in chordates much earlier than previously thought, and exemplify the importance of detailed analysis of whole-genome draft sequence to provide new insights into gene evolution.
The use of Open Reading frame ESTs (ORESTES) for analysis of the honey bee transcriptome
Authors: Nunes Francis MF , Valente Valeria , Sousa Josane F , Cunha Marco AV , Pinheiro Daniel G , Maia Rafaela M , Araujo Daniela D , Costa Maria CR , Martins Waleska K , Carvalho Alex F , Monesi Nadia , Nascimento Adriana M , Peixoto Pablo MV , Silva Maria FR , Ramos Ricardo GP , Reis Luis FL , Dias-Neto Emmanuel , Souza Sandro J , Simpson Andrew JG , Zago Marco A , Soares Ademilson EE , Bitondi Marcia MG , Espreafico Enilza M , Espindola Foued S , Paco-Larson Maria L , Simoes Zila LP , Hartfelder Klaus , Silva Wilson A
Published: November 2004

Background

The ongoing efforts to sequence the honey bee genome require additional initiatives to define its transcriptome. Towards this end, we employed the Open Reading frame ESTs (ORESTES) strategy to generate profiles for the life cycle of Apis mellifera workers.

Results

Of the 5,021 ORESTES, 35.2% matched with previously deposited Apis ESTs. The analysis of the remaining sequences defined a set of putative orthologs whose majority had their best-match hits with Anopheles and Drosophila genes. CAP3 assembly of the Apis ORESTES with the already existing 15,500 Apis ESTs generated 3,408 contigs. BLASTX comparison of these contigs with protein sets of organisms representing distinct phylogenetic clades revealed a total of 1,629 contigs that Apis mellifera shares with different taxa. Most (41%) represent genes that are in common to all taxa, another 21% are shared between metazoans (Bilateria), and 16% are shared only within the Insecta clade. A set of 23 putative genes presented a best match with human genes, many of which encode factors related to cell signaling/signal transduction. 1,779 contigs (52%) did not match any known sequence. Applying a correction factor deduced from a parallel analysis performed with Drosophila melanogaster ORESTES, we estimate that approximately half of these no-match ESTs contigs (22%) should represent Apis-specific genes.

Conclusions

The versatile and cost-efficient ORESTES approach produced minilibraries for honey bee life cycle stages. Such information on central gene regions contributes to genome annotation and also lends itself to cross-transcriptome comparisons to reveal evolutionary trends in insect genomes.
Thymus-derived glucocorticoids are insufficient for normal thymus homeostasis in the adult mouse
Authors: Pruett Stephen B , Padgett Eric L
Published: November 2004

Background

It is unclear if thymus-derived glucocorticoids reach sufficient local concentrations to support normal thymus homeostasis, or if adrenal-derived glucocorticoids from the circulation are required. Modern approaches to this issue (transgenic mice that under or over express glucocorticoid receptor in the thymus) have yielded irreconcilably contradictory results, suggesting fundamental problems with one or more the transgenic mouse strains used. In the present study, a more direct approach was used, in which mice were adrenalectomized with or without restoration of circulating corticosterone using timed release pellets. Reversal of the increased number of thymocytes caused by adrenalectomy following restoration of physiological corticosterone concentrations would indicate that corticosterone is the major adrenal product involved in thymic homeostasis.

Results

A clear relationship was observed between systemic corticosterone concentration, thymus cell number, and percentage of apoptotic thymocytes. Physiological concentrations of corticosterone in adrenalectomized mice restored thymus cell number to normal values and revealed differential sensitivity of thymocyte subpopulations to physiological and stress-inducible corticosterone concentrations.

Conclusion

This indicates that thymus-derived glucocorticoids are not sufficient to maintain normal levels of death by neglect in the thymus, but that apoptosis and possibly other mechanisms induced by physiological, non stress-induced levels of adrenal-derived corticosterone are responsible for keeping the total number of thymocytes within the normal range.
A common genetic factor underlies hypertension and other cardiovascular disorders
Authors: Williams Frances MK , Cherkas Lynn F , Spector Tim D , MacGregor Alex J
Published: November 2004

Background

Certain conditions characterised by blood vessel occlusion or vascular spasm have been found to cluster together in epidemiological studies. However the biological causes for these associations remain controversial. This study used a classical twin design to examine whether these conditions are linked through shared environmental exposures or by a common underlying genetic propensity to vasospasm.

Methods

We investigated the association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease in twins from a national register. Phenotype status was determined using a questionnaire and the genetic and environmental association between phenotypes was estimated through variance components analysis.

Results

Responses were obtained from 2,204 individuals comprising 525 monozygotic and 577 dizygotic pairs. There was a significant genetic contribution to all four traits with heritabilities ranging from 0.34 to 0.64. Multivariate model-fitting demonstrated that a single common genetic factor underlies the four conditions.

Conclusions

We have confirmed an association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease, and shown that a single genetic factor underlies them. The demonstration of a shared genetic factor explains the association between them and adds weight to the theory of an inherited predisposition to vasospasm.
Elevated serum procollagen type III peptide in splanchnic and peripheral circulation of patients with inflammatory bowel disease submitted to surgery
Authors: De Simone Matilde , Cioffi Ugo , Contessini-Avesani Ettore , Oreggia Barbara , Paliotti Roberta , Pierini Alberto , Bolla Gianni , Oggiano Elide , Ferrero Stefano , Magrini Fabio , Ciulla Michele M
Published: November 2004

Background

In the hypothesis that the increased collagen metabolism in the intestinal wall of patients affected by inflammatory bowel disease (IBD) is reflected in the systemic circulation, we aimed the study to evaluate serum level of procollagen III peptide (PIIIP) in peripheral and splanchnic circulation by a commercial radioimmunoassay of patients with different histories of disease.

Methods

Twenty-seven patients, 17 with Crohn and 10 with ulcerative colitis submitted to surgery were studied. Blood samples were obtained before surgery from a peripheral vein and during surgery from the mesenteric vein draining the affected intestinal segment. Fifteen healthy age and sex matched subjects were studied to determine normal range for peripheral PIIIP.

Results

In IBD patients peripheral PIIIP level was significantly higher if compared with controls (5.0 ± 1.9 vs 2.7 ± 0.7 μg/l; p = 0.0001); splanchnic PIIIP level was 5.5 ± 2.6 μg/l showing a positive gradient between splanchnic and peripheral concentrations of PIIIP. No significant differences between groups nor correlations with patients' age and duration of disease were found.

Conclusions

We provide evidence that the increased local collagen metabolism in active IBD is reflected also in the systemic circulation irrespective of the history of the disease, suggesting that PIIIP should be considered more appropiately as a marker of the activity phases of IBD.
Lipoprotein lipase in hemodialysis patients: indications that low molecular weight heparin depletes functional stores, despite low plasma levels of the enzyme
Authors: Näsström Birgit , Stegmayr Bernd , Olivecrona Gunilla , Olivecrona Thomas
Published: November 2004

Background

Lipoprotein lipase (LPL) has a central role in the catabolism of triglyceride-rich lipoproteins. The enzyme is anchored to the vascular endothelium through interaction with heparan sulphate proteoglycans and is displaced from this interaction by heparin. When heparin is infused, there is a peak of LPL activity accompanied by a reduction in triglycerides (TG) during the first hour, followed by a decrease in LPL activity to a stable plateau during the remaining session while TG increase towards and beyond baseline. This suggests that tissue stores of LPL become depleted. It has been argued that low molecular weight (LMW) heparins cause less disturbance of the LPL system than conventional heparin does.

Methods

We have followed LPL activity and TG during a dialysis-session with a LMW heparin (dalteparin) using the same patients and regime as in a previous study with conventional heparin, i.e. a primed infusion.

Results

The shape of the curve for LPL activity resembled that during the earlier dialyses with conventional heparin, but the values were lower during dialysis with dalteparin. The area under the curve for LPL activity during the peak period (0–180 minutes) was only 27% and for the plateau period (180–240 minutes) it was only 36% of that observed with conventional heparin (p < 0.01). These remarkably low plasma LPL activities prompted us to re-analyze LPL activity and to measure LPL mass in frozen samples from our earlier studies. There was excellent correlation between the new and old values which rules out the possibility of assay variations as a confounding factor. TG increased from 2.14 mmol/L before, to 2.59 mmol/L after the dialysis (p < 0.01). From 30 minutes on, the TG values were significantly higher after dalteparin compared to conventional heparin (p < 0.05).

Conclusion

These results indicate that LMW heparins disturb the LPL system as much or more than conventional heparin does.
Low birth weight and longitudinal trends of cardiovascular risk factor variables from childhood to adolescence: the bogalusa heart study
Authors: Frontini Maria G , Srinivasan Sathanur R , Xu Jihua , Berenson Gerald S
Published: November 2004

Background

Several studies have linked low birth weight to adverse levels of cardiovascular risk factors and related diseases. However, information is sparse at a community level in the U.S. general population regarding the effects of low birth weight on the longitudinal trends in cardiovascular risk factor variables measured concurrently from childhood to adolescence.

Methods

Longitudinal analysis was performed retrospectively on data collected from the Bogalusa Heart Study cohort (n = 1141; 57% white, 43% black) followed from childhood to adolescence by repeated surveys between 1973 and 1996. Subjects were categorized into low birth weight (below the race-specific 10th percentile; n = 123) and control (between race-specific 50–75th percentile; n = 296) groups.

Results

Low birth weight group vs control group had lower mean HDL cholesterol (p = 0.05) and higher LDL cholesterol (p = 0.05) during childhood (ages 4–11 years); higher glucose (p = 0.02) during adolescence. Yearly rates of change from childhood to adolescence in systolic blood pressure (p = 0.02), LDL cholesterol (p = 0.05), and glucose (p = 0.07) were faster, and body mass index (p = 0.03) slower among the low birth weight group. In a multivariate analysis, low birth weight was related independently and adversely to longitudinal trends in systolic blood pressure (p = 0.004), triglycerides (p = 0.03), and glucose (p = 0.07), regardless of race or gender. These adverse associations became amplified with age.

Conclusions

Low birth weight is characterized by adverse developmental trends in metabolic and hemodynamic variables during childhood and adolescence; and thus, it may be an early risk factor in this regard.
Dual practice in the health sector: review of the evidence
Authors: Ferrinho Paulo , Van Lerberghe Wim , Fronteira Inês , Hipólito Fátima , Biscaia André
Published: November 2004

This paper reports on income generation practices among civil servants in the health sector, with a particular emphasis on dual practice. It first approaches the subject of public–private overlap. Thereafter it focuses on coping strategies in general and then on dual practice in particular.

To compensate for unrealistically low salaries, health workers rely on individual coping strategies. Many clinicians combine salaried, public-sector clinical work with a fee-for-service private clientele. This dual practice is often a means by which health workers try to meet their survival needs, reflecting the inability of health ministries to ensure adequate salaries and working conditions.

Dual practice may be considered present in most countries, if not all. Nevertheless, there is surprisingly little hard evidence about the extent to which health workers resort to dual practice, about the balance of economic and other motives for doing so, or about the consequences for the proper use of the scarce public resources dedicated to health.

In this paper dual practice is approached from six different perspectives: (1) conceptual, regarding what is meant by dual practice; (2) descriptive, trying to develop a typology of dual practices; (3) quantitative, trying to determine its prevalence; (4) impact on personal income, the health care system and health status; (5) qualitative, looking at the reasons why practitioners so frequently remain in public practice while also working in the private sector and at contextual, personal life, institutional and professional factors that make it easier or more difficult to have dual practices; and (6) possible interventions to deal with dual practice.
The impact of antidepressant treatment on population health: synthesis of data from two national data sources in Canada
Authors: Patten Scott B
Published: November 2004

Background

In randomized, controlled trials, antidepressant medications have been shown to reduce the duration of major depressive episodes and to reduce the frequency of relapse during long-term treatment. The epidemiological impact of antidepressant use on episode duration and relapse frequency, however, has not been described.

Methods

Data from two Canadian general health surveys were used in this analysis: the National Population Health Survey (NPHS) and the Canadian Community Health Survey (CCHS). The NPHS is a longitudinal study that collected data between 1994 and 2000. These longitudinal data allowed an approximation of episode incidence to be calculated. The cross-sectional CCHS allowed estimation of episode duration. The surveys used the same sampling frame and both incorporated a Short Form version of the Composite International Diagnostic Interview.

Results

Episodes occurring in antidepressant users lasted longer than those in non-users. The apparent incidence of major depressive episodes among those taking antidepressants was higher than that among respondents not taking antidepressants. Changes in duration and incidence over the data collection interval were not observed.

Conclusions

The most probable explanation for these results is confounding by indication and/or severity: members of the general population who are taking antidepressants probably have more highly recurrent and more severe mood disorders. In part, this may have been due to the use of a brief predictive diagnostic interview, which may be prone to detection of sub-clinical cases. Whereas antidepressant use increased considerably over the data-collection period, differences in episode incidence and duration over time were not observed. This suggests that the impact of antidepressant medications on population health may have been less than expected.
Statistical design considerations for pilot studies transitioning therapies from the bench to the bedside
Authors: Carter Rickey E , Woolson Robert F
Published: November 2004

Pilot studies are often used to transition therapies developed using animal models to a clinical setting. Frequently, the focus of such trials is on estimating the safety in terms of the occurrence of certain adverse events. With relatively small sample sizes, the probability of observing even relatively common events is low; however, inference on the true underlying event rate is still necessary even when no events of interest are observed. The exact upper limit to the event rate is derived and illustrated graphically. In addition, the simple algebraic expression for the confidence bound is seen to be useful in the context of planning studies.