bluuebunny/crossref_metadata_2025 huggingface dataset:
ASAP: analysis of peptide composition
Authors: Serra-Hartmann Xavier , Rebordosa Xavier , Piñol Jaume , Querol Enrique , Martı́-Renom Marc

A.
Published: July 2002

Summary: ASAP is a web tool designed to search for specific dipeptides, tripeptides and tetrapeptides in a protein sequence database. The server allows for: (a) identification of frequent and infrequent peptides and the creation of peptide probability tables for a given database of sequences (GenerNet program), (b) determination of the compatibility of an amino-acid sequence to the given peptide probability tables (ClonErrNet program); and (c) comparison of different protein databases based on peptide composition (CompNet program). ASAP server can be useful in protein engineering and/or protein classification studies.

Availability: http://guitar.rockefeller.edu/~marcius/ASAP.html

Contact: martim@rockefeller.edu

* To whom correspondence should be addressed.
Storing biological sequence databases in relational form
Authors: Xie Guochun , DeMarco Reynold , Blevins Richard , Wang Yuhong
Published: July 2002

Summary: We have created a set of applications using Perl and Java in combination with XML technology to install biological sequence databases into an Oracle RDBMS. An easy-to-use interface using Java has been created for database query and other tools developed to integrate with our in-house bioinformatics applications.

Availability: The database schema, DTD file, and source codes are available from the authors via email.

Contact: guochun_xie@merck.com
GESTALT: a workbench for automatic integration and
visualization of large-scale genomic sequence analyses
Authors: Glusman Gustavo , Lancet Doron
Published: July 2002

Summary: The GESTALT Workbench is a WWW-based tool for genomic sequence analysis, comparison and annotation, with strong emphasis on visualization. GESTALT integrates graphically the output of diverse sequence analysis algorithms producing an information-rich, interactive genomic map.

Availability: The GESTALT Workbench, as well as a more detailed description, are available at http://bioinfo.weizmann.ac.il/GESTALT/.

Contact: Gustavo@bioinfo.weizmann.ac.il, Doron.Lancet@weizmann.ac.il
Viral Genome DataBase: storing and analyzing genes and proteins
from complete viral genomes
Authors: Hiscock David , Upton Chris
Published: July 2002

* To whom correspondence should be addressed.

Summary: The Viral Genome DataBase (VGDB) contains detailed information of the genes and predicted protein sequences from 15 completely sequenced genomes of large (&100 kb) viruses (2847 genes). The data that is stored includes DNA sequence, protein sequence, GenBank and user-entered notes, molecular weight (MW), isoelectric point (pI), amino acid content, A + T%, nucleotide frequency, dinucleotide frequency and codon use. The VGDB is a mySQL database with a user-friendly JAVA GUI. Results of queries can be easily sorted by any of the individual parameters.

Availability: The software and additional figures and information are available at http://athena.bioc.uvic.ca/genomes/index.html.

Contact: cupton@uvic.ca
Browsing the SLoop database of structurally classified loops connecting elements of protein secondary structure
Authors: Burke David F. , Deane Charlotte M. , Blundell Tom L.
Published: July 2002

We describe a web server, which provides easy access to the SLoop database of loop conformations connecting elements of protein secondary structure. The loops are classified according to their length, the type of bounding secondary structures and the conformation of the mainchain. The current release of the database consists of over 8000 loops of up to 20 residues in length. A loop prediction method, which selects conformers on the basis of the sequence and the positions of the elements of secondary structure, is also implemented. These web pages are freely accessible over the internet at http://www-cryst.bioc.cam.ac.uk/~sloop.
IMpRH Server: an RH mapping server available on the Web
Authors: Milan Denis , Hawken Rachel , Cabau Cédric , Leroux Sophie , Genet Carine , Lahbib Yvette , Tosser Gwenola , Robic Annie , Hatey Francois , Alexander Lee , Beattie Craig , Schook Larry , Yerle Martine , Gellin Joël
Published: July 2002

Summary: The INRA-Minnesota Porcine Radiation Hybrid (IMpRH) Server provides both a mapping tool (IMpRH mapping tool) and a database (IMpRH database) of officially submitted results. The mapping tool permits the mapping of a new marker relatively to markers previously mapped on the IMpRH panel. The IMpRH database is the official database for submission of new results and queries. The database not only permits the sharing of public data but also semi-private and private data.

Availability: http://imprh.toulouse.inra.fr

Contact: milan@toulouse.inra.fr

Supplementary Information: Details can be found at http://www.toulouse.inra.fr/lgc/pig/RH/help/help.htm
eSAGE: managing and analysing data generated with Serial
Analysis of Gene Expression (SAGE)
Authors: Margulies Elliott H. , Innis Jeffrey W.
Published: July 2002

Summary: eSAGE is a comprehensive set of software tools for managing and analysing data generated with Serial Analysis of Gene Expression (SAGE).

Availability: eSAGE is freely available for non-commercial use.

Contact: ehm@umich.edu
MDB: a database system utilizing automatic construction of
modules and STAR-derived universal language
Authors: Migliavacca Eugenia , Adzhubei Alexei A. , Peitsch Manuel C.
Published: July 2002

Motivation: The value of information greatly increases if stored in databases. The objective was to construct a multi-purpose database system primarily designed to store and provide access to three-dimensional structures of biological molecules including theoretical models.

Results: A dictionary defining data format and structure for three-dimensional models of biological molecules (MDB dictionary) was developed. The dictionary was written using universal, standardized data description language. This language can be applied to describe data with no restrictions on their origin or type, including metadata. Thus both the data definitions (format) and database descriptions are created using the uniform language and processed with universal software. A database and data design technique that allowed use of dictionaries to automatically construct relational databases was developed. This technique was employed to construct the MDB database system. Data design developed and applied in the MDB project makes it possible to carry out data curation utilizing the database engine to identify errors. It also allows storage and query of data at different levels of consistency with the standard format specifications, i.e. both the correctly formatted data, and data that requires further curation.

Availability: The MDB dictionary is available at http://www.gwer.ch/proteinstructure/mdb and as part of the PDB resources at http://pdb.rutgers.edu/mmcif/.

Contact: aaa75196@gsk.com; em96794@gsk.com

* A.A.A. and E.M. are joint first authors.

1 To whom correspondence should be addressed.
Virtual PCR
Authors: Lexa M. , Horak J. , Brzobohaty B.
Published: July 2002

Summary: We present an algorithm that uses public sequence data to predict PCR products. The algorithm is implemented as a CGI script. Output is compared to real-world PCR.

Availability: Perl code and instructions for installation are freely available over the internet at http://www.sci.muni.cz/LMFR/vpcr.html

Contact: m-lexa@sci.muni.cz

* To whom correspondence should be addressed.
COMBOSA3D: combining sequence alignments with three-dimensional

structures
Authors: Stothard P. M.
Published: July 2002

Summary: COMBOSA3D is a program that allows sequence conservation to be viewed in its proper three-dimensional environment. It superimposes sequence alignment information onto a protein structure using a customizable color scheme, which is also applied to a textual sequence alignment for reference.

Availability: The program can be tested at http://www.bioinformatics.org/combosa3d/, and the source code is freely available.

Contact: stothard@ualberta.ca

Supplementary information: Additional COMBOSA3D documentation is available at the above URL.
RCNPRED: prediction of the residue co-ordination numbers in

proteins
Authors: Fariselli Piero , Casadio Rita
Published: July 2002

Summary: The RCNPRED server implements a neural network-based method to predict the co-ordination numbers of residues starting from the protein sequence. Using evolutionary information as input, RCNPRED predicts the residue states of the proteins in the database with 69% accuracy and scores 12 percentage points higher than a simple statistical method. Moreover the server implements a neural network to predict the relative solvent accessibility of each residue. A protein sequence can be directly submitted to RCNPRED: residue co-ordination numbers and solvent accessibility for each chain are returned via e-mail.

Availability: Freely available to non-commercial users at http://prion.biocomp.unibo.it/rcnpred.html

Contact: casadio@alma.unibo.it; piero@lipid.biocomp.unibo.it

* To whom the correspondence should be addressed.
MetaFam: a unified classification of protein families. I.

Overview and statistics
Authors: Silverstein Kevin A. T. , Shoop Elizabeth , Johnson James E. , Retzel Ernest F.
Published: July 2002

Motivation: Protein sequence classification is becoming an increasingly important means of organizing the voluminous data produced by large-scale genome sequencing projects. At present, there are several independent classification methods. To aid the general classification effort, we have created a unified protein family resource, MetaFam. MetaFam is a protein family classification built upon 10 publicly-accessible protein family databases (Blocks\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(+\) \end{document}, DOMO, Pfam, PIR-ALN, PRINTS, PROSITE, ProDom, PROTOMAP, SBASE, and SYSTERS). MetaFam’s family ‘supersets’, as we call them, are created automatically using set-theory to compare families among the databases. Families of one database are matched to those in another when the intersection of their members exceeds all other possible family pairings between the two databases. Pairwise family matches are drawn together transitively to create a new list of protein family supersets.

Results: MetaFam family supersets have several useful features: (1) each superset contains more members than the families from which it is composed, because each of the component family databases only works with a subset of our full non-redundant set of proteins; (2) conflicting assignments can be pinpointed quickly, since our analysis identifies individual members that are in conflict with the majority consensus; (3) family descriptions that are absent from automated databases can frequently be assigned; (4) statistics have been computed comparing domain boundaries, family size distributions, and overall quality of MetaFam supersets; (5) the supersets have been loaded into a relational database to allow for complex queries and visualization of the connections among families in a superset and the consensus of individual domain members; and (6) the quality of individual supersets has been assessed using numerous quantitative measures such as family consistency, connectedness, and size. We anticipate this new resource will be particularly useful to genomic database curators.

Availability: Free access to the MetaFam web server is provided to all users at http://metafam.ahc.umn.edu/.

Contact: metafam@ahc.umn.edu

Supplementary information: Detailed distribution plots on MetaFam 2.0 supersets and its constituent family databases (e.g. superset/family sizes, domain boundary comparisons) are shown at http://metafam.ahc.umn.edu/mf2.0/stats.html. Statistics on the current release of MetaFam can be found at http://metafam.ahc.umn.edu/current_release/stats.html.

* To whom correspondence should be addressed.
A new approach to sequence comparison: normalized sequence
alignment
Authors: Arslan Abdullah N. , Eğecioğlu Ömer , Pevzner Pavel A.
Published: July 2002

The Smith–Waterman algorithm for local sequence alignment is one of the most important techniques in computational molecular biology. This ingenious dynamic programming approach was designed to reveal the highly conserved fragments by discarding poorly conserved initial and terminal segments. However, the existing notion of local similarity has a serious flaw: it does not discard poorly conserved intermediate segments. The Smith–Waterman algorithm finds the local alignment with maximal score but it is unable to find local alignment with maximum degree of similarity (e.g. maximal percent of matches). Moreover, there is still no efficient algorithm that answers the following natural question: do two sequences share a (sufficiently long) fragment with more than 70% of similarity? As a result, the local alignment sometimes produces a mosaic of well-conserved fragments artificially connected by poorly-conserved or even unrelated fragments. This may lead to problems in comparison of long genomic sequences and comparative gene prediction as recently pointed out by Zhang et al. (Bioinformatics , 15, 1012–1019, 1999). In this paper we propose a new sequence comparison algorithm (normalized local alignment ) that reports the regions with maximum degree of similarity. The algorithm is based on fractional programming and its running time is \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(O(n^{2}\mathrm{log}n)\) \end{document}. In practice, normalized local alignment is only 3–5 times slower than the standard Smith–Waterman algorithm.

Contact: {arslan,omer}@cs.ucsb.edu; ppevzner@cs.ucsd.edu
NIFAS: visual analysis of domain evolution in proteins
Authors: Storm Christian E. V. , Sonnhammer Erik L. L.
Published: July 2002

Motivation: Multi-domain proteins have evolved by insertions or deletions of distinct protein domains. Tracing the history of a certain domain combination can be important for functional annotation of multi-domain proteins, and for understanding the function of individual domains. In order to analyze the evolutionary history of the domains in modular proteins it is desirable to inspect a phylogenetic tree based on sequence divergence with the modular architecture of the sequences superimposed on the tree.

Result: A Java applet, NIFAS, that integrates graphical domain schematics for each sequence in an evolutionary tree was developed. NIFAS retrieves domain information from the Pfam database and uses CLUSTAL W to calculate a tree for a given Pfam domain. The tree can be displayed with symbolic bootstrap values, and to allow the user to focus on a part of the tree, the layout can be altered by swapping nodes, changing the outgroup, and showing/collapsing subtrees. NIFAS is integrated with the Pfam database and is accessible over the internet (http://www.cgr.ki.se/Pfam). As an example, we use NIFAS to analyze the evolution of domains in Protein Kinases C.

Contact: christian.storm@cgr.ki.se
Construction of DNA restriction maps based on a simplified

experiment
Authors: Błażewicz J. , Formanowicz P. , Kasprzak M. , Jaroszewski M. , Markiewicz W. T.
Published: July 2002

Motivation: A formulation of a new problem of the restriction map construction based on a simplified digestion experiment and a development of an algorithm for solving both ideal and noisy data cases of the introduced problem.

Results: A simplified partial digest problem and a branch and cut algorithm for finding the solution of the problem.

Contact: blazewic@sol.put.poznan.pl

* To whom correspondence should be addressed.

† Fellowship holder of the Foundation for Polish Sciences.
SVDMAN—singular value decomposition analysis of

microarray data
Authors: Wall Michael E. , Dyck Patricia A. , Brettin Thomas S.
Published: July 2002

Summary: We have developed two novel methods for Singular Value Decomposition analysis (SVD) of microarray data. The first is a threshold-based method for obtaining gene groups, and the second is a method for obtaining a measure of confidence in SVD analysis. Gene groups are obtained by identifying elements of the left singular vectors, or gene coefficient vectors, that are greater in magnitude than the threshold \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(WN^{{-}1/2}\) \end{document}, where \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(N\) \end{document}is the number of genes, and \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(W\) \end{document}is a weight factor whose default value is 3. The groups are non-exclusive and may contain genes of opposite (i.e. inversely correlated) regulatory response. The confidence measure is obtained by systematically deleting assays from the data set, interpolating the SVD of the reduced data set to reconstruct the missing assay, and calculating the Pearson correlation between the reconstructed assay and the original data. This confidence measure is applicable when each experimental assay corresponds to a value of parameter that can be interpolated, such as time, dose or concentration. Algorithms for the grouping method and the confidence measure are available in a software application called SVD Microarray ANalysis (SVDMAN). In addition to calculating the SVD for generic analysis, SVDMAN provides a new means for using microarray data to develop hypotheses for gene associations and provides a measure of confidence in the hypotheses, thus extending current SVD research in the area of global gene expression analysis.

Availability: ftp://bpublic.lanl.gov/compbio/software

Contact: brettin@lanl.gov

Supplementary information: http://home.lanl.gov/svdman

* To whom correspondence should be addressed.
LDB2000: sequence-based integrated maps of the human genome
Authors: Ke Xiayi , Tapper William , Collins Andrew
Published: July 2002

Motivation: Integrated maps are useful for gene mapping and establishing the relationship between recombination and sequence. In this paper we describe algorithms and their implementation for constructing sequence-based integrated maps of the human chromosomes, which are presented in LDB2000, a web based resource. Gene mapping efforts are now focussing on linkage disequilibrium mapping and extension of the integrated map to represent the extent of linkage disequilibrium in different genomic regions would further increase the utility of these maps.

Results: Sequence-based integrated maps have been completed for chromosomes 21 and 22. These maps provide locations for genes and polymorphic markers in sequence and on genetic linkage, radiation hybrid and cytogenetic scales. Single nucleotide polymorphisms associated with genes in the maps are also included and their sequence locations indicated. Related locus information, such as aliases and expression information, can be searched on the WWW site.

Availability: http://cedar.genetics.soton.ac.uk/public_html/LDB2000.html

Contact: arc@soton.ac.uk
MEDUSA: large scale automatic selection and visual assessment
of PCR primer pairs
Authors: Podowski Raf M. , Sonnhammer Erik L. L.
Published: July 2002

Summary: MEDUSA is a tool for automatic selection and visual assessment of PCR primer pairs, developed to assist large scale gene expression analysis projects. The system allows specification of constraints of the location and distances between the primers in a pair. For instance, primers in coding, non-coding, exon/intron-spanning regions might be selected. Medusa applies these constraints as a filter to primers predicted by three external programs, and displays the resulting primer pairs graphically in the Blixem (Sonnhammer and Durbin, Comput. Appl. Biosci.10, 301–307, 1994; http://www.cgr.ki.se/cgr/groups/sonnhammer/Blixem.html) viewer.

Availability: The MEDUSA web server is available at http://www.cgr.ki.se/cgr/MEDUSA. The source code and user information are available at ftp://ftp.cgr.ki.se/pub/prog/medusa.

Contact: Erik.Sonnhammer@cgr.ki.se
Representation of amino acids as five-bit or three-bit patterns
for filtering protein databases
Authors: Coghlan Avril , Mac
   Dónaill Dónall A. , Buttimore Nigel H.
Published: July 2002

Motivation: We propose representing amino acids by bit-patterns so they may be used in a filter algorithm for similarity searches over protein databases, to rapidly eliminate non-homologous regions of database sequences. The filter algorithm would be based on dynamic programming optimization. It would have the advantage over previous filter algorithms that its substitution scoring function distinguishes between conservative and non-conservative amino acid substitutions.

Results: Simulated annealing was used to search for the best five-bit or three-bit patterns to represent amino acids, where similar amino acids were given similar bit-patterns. The similarity between amino acids was estimated from the BLOSUM45 matrix. Representing amino acids by these five-bit and three-bit patterns, the Escherichia coli PhoE precursor and the bacteriophage PA2 LC precursor were aligned. The alignments were nearly the same as that obtained when BLOSUM45 was used to score substitutions.

Availability: The C code of the optimization algorithm for searching for the optimal bit-pattern representation of amino acids is available from the authors upon request.

Contact: dmcdonll@tcd.ie

* To whom correspondence should be addressed.
Amino acid similarity matrices based on force fields
Authors: Dosztányi Zsuzsanna , Torda Andrew E.
Published: July 2002

Motivation: We propose a general method for deriving amino acid substitution matrices from low resolution force fields. Unlike current popular methods, the approach does not rely on evolutionary arguments or alignment of sequences or structures. Instead, residues are computationally mutated and their contribution to the total energy/score is collected. The average of these values over each position within a set of proteins results in a substitution matrix.

Results: Example substitution matrices have been calculated from force fields based on different philosophies and their performance compared with conventional substitution matrices. Although this can produce useful substitution matrices, the methodology highlights the virtues, deficiencies and biases of the source force fields. It also allows a rather direct comparison of sequence alignment methods with the score functions underlying protein sequence to structure threading.

Availability: Example substitution matrices are available from http://www.rsc.anu.edu.au/~zsuzsa/suppl/matrices.html.

Supplementary information: The list of proteins used for data collection and the optimized parameters for the alignment are given as supplementary material at http://www.rsc.anu.edu.au/~zsuzsa/suppl/matrices.html.

Contact: zsuzsa@rsc.anu.edu.au

* To whom correspondence should be addressed.
A fast top–down method for constructing reliable
radiation hybrid frameworks
Authors: Bø Trond H. , Jonassen Inge , Eidhammer Ingvar , Helgesen Carsten
Published: July 2002

Motivation: Radiation Hybrid Mapping (RHM) is a technique used to order a set of markers on a genome and estimating physical distances between them. RHM provides information on marker placement independent from other methods such as sequencing, and can therefore be used for example in genome sequencing to help ordering contigs. A radiation hybrid framework can be constructed by choosing a set of markers so that the chromosome coverage is good and so that the markers can be ordered with high confidence. Automatically constructing RHM frameworks is a computationally challenging problem.

Results: We have developed a new method for constructing radiation hybrid frameworks. Given a relatively large set of markers for a chromosome, the algorithm aims to select an ordered subset that makes up a framework, and that contains as many markers as possible. The algorithm has a time complexity that is better than any of the existing methods that we are aware of. Furthermore, we propose a method for comparing if two frameworks are consistent, giving a visual presentation as well as quantitative measures of how well the two frameworks agree. Applying our method on marker sets from 22 human chromosomes and comparing the resulting frameworks with previously published frameworks, we demonstrate that our automatic method efficiently constructs frameworks with good coverage of each chromosome and with high degree of agreement on the marker ordering.

Availability: The software is available from the authors.

Supplementary information: MCST paths, frameworks and plots are available at http://www.ii.uib.no/~trondb/RHmapping/

Contact: trondb@ii.uib.no

* To whom correspondence should be addressed.
A viral sampling design for testing the molecular clock and for
estimating evolutionary rates and divergence times
Authors: Seo Tae-Kun , Thorne Jeffrey L. , Hasegawa Masami , Kishino Hirohisa
Published: July 2002

Motivation: The high pace of viral sequence change means that variation in the times at which sequences are sampled can have a profound effect both on the ability to detect trends over time in evolutionary rates and on the power to reject the Molecular Clock Hypothesis (MCH). Trends in viral evolutionary rates are of particular interest because their detection may allow connections to be established between a patient’s treatment or condition and the process of evolution. Variation in sequence isolation times also impacts the uncertainty associated with estimates of divergence times and evolutionary rates. Variation in isolation times can be intentionally adjusted to increase the power of hypothesis tests and to reduce the uncertainty of evolutionary parameter estimates, but this fact has received little previous attention.

Results: We provide approximations for the power to reject the MCH when the alternative is that rates change in a linear fashion over time and when the alternative is that rates differ randomly among branches. In addition, we approximate the standard deviation of estimated evolutionary rates and divergence times. We illustrate how these approximations can be exploited to determine which viral sample to sequence when samples representing different dates are available.

Contact: seo@ism.ac.jp; thorne@statgen.ncsu.edu; hasegawa@ism.ac.jp; kishino@wheat.ab.a.u-tokyo.ac.jp

* To whom correspondence should be addressed.
Machine learning of functional class from phenotype data
Authors: Clare Amanda , King Ross D.
Published: July 2002

Motivation: Mutant phenotype growth experiments are an important novel source of functional genomics data which have received little attention in bioinformatics. We applied supervised machine learning to the problem of using phenotype data to predict the functional class of Open Reading Frames (ORFs) in Saccaromyces cerevisiae. Three sources of data were used: TRansposon-Insertion Phenotypes, Localization and Expression in Saccharomyces (TRIPLES), European Functional Analysis Network (EUROFAN) and Munich Information Center for Protein Sequences (MIPS). The analysis of the data presented a number of challenges to machine learning: multi-class labels, a large number of sparsely populated classes, the need to learn a set of accurate rules (not a complete classification), and a very large amount of missing values. We modified the algorithm C4.5 to deal with these problems.

Results: Rules were learnt which are accurate and biologically meaningful. The rules predict function of 83 ORFs of unknown function at an estimated accuracy of ⩾ 80%.

Availability: The data and complete results are available at http://users.aber.ac.uk/ajc99/phenotype/.

Contact: ajc99@aber.ac.uk
Calculating the SNP-effective sample size from an alignment
Authors: Haubold Bernhard , Wiehe Thomas
Published: July 2002

Motivation: The number of Single Nucleotide Polymorphisms (SNPs) detectable in an alignment is a function of the length and the number of the aligned sequences. The latter is called sample size. However, a typical alignment, for instance obtained as a BLAST-search result of a query sequence against an EST database, does not evenly cover the query sequence. Therefore, it is usually not clear what the actual sample size is.

Results: We present a method to calculate the effective sample size, called neff, for a given BLAST alignment. This method takes into account that multiple coverage contributes only logarithmically to the SNP yield of a given sequence stretch. We show that the effective sample size neff is usually much smaller than would be expected for a given amount of coverage and illustrate this with two typical examples.

Availability: The algorithm is implemented in NEFF, a program written in FORTRAN90 that is accessible at http://soft.ice.mpg.de/neff. From this site also the source, except for two subroutines protected by copyright, and a LINUX compiled executable can be downloaded.

Contact: twiehe@ice.mpg.de

* To whom correspondence should be addressed.

2 Present address: LION Bioscience AG, Heidelberg, Germany.
Extracting transcriptional events from temporal gene expression
patterns during Dictyostelium development
Authors: S̆ás̆ik R. , Iranfar N. , Hwa T. , Loomis W. F.
Published: July 2002

Motivation: The DNA microarray technology can generate a large amount of data describing the time-course of gene expression. These data, when properly interpreted, can yield a great deal of information concerning differential gene expression during development. Much current effort in bioinformatics has been devoted to the analysis of gene expression data, usually via some ‘clustering analysis’ on the raw data in some abstract high dimensional space. Here, we describe a method where we first ‘process’ the raw time-course data using a simple biologically based kinetic model of gene expression. This allows us to reduce the vast data to a few vital attributes characterizing each expression profile, e.g. the times of the onset and cessation of the expression of the developmentally regulated genes. These vital attributes can then be trivially clustered by visual inspection to reveal biologically significant effects.

Results: We have applied this approach to microarray expression data from samples isolated every 2 h throughout the 24 h developmental program of Dictyostelium discoideum. mRNA accumulation patterns for 50 developmental genes were found to fit the kinetic model with a p-value of 0.05 or better. Transcription of these genes appears to be initiated in bursts at well-defined periods during development, in a manner suggestive of a dependent sequence. This approach can be applied to analyses of other temporal gene expression patterns, including those of the cell cycle.

Contact: sasik@physics.ucsd.edu

Supplementary information: Intensity ratios for all genes in this study are available at http://www.biology.ucsd.edu/loomis-cgi/microarray/index.html.

* To whom correspondence should be addressed.
MaxBench: evaluation of sequence and structure comparison
methods
Authors: Leplae Raphael , Hubbard Tim J. P.
Published: July 2002

Summary: MaxBench is a web-based system available for evaluating the results of sequence and structure comparison methods, based on the SCOP protein domain classification. The system makes it easy for developers to both compare the overall performance of their methods to standard algorithms and investigate the results of individual comparisons.

Availability: http://www.sanger.ac.uk/Users/lp1/MaxBench/

Contact: lp1@sanger.ac.uk

* To whom correspondence should be addressed.
Extraction of knowledge on protein--protein interaction
by association rule discovery
Authors: Oyama T. , Kitano K. , Satou K. , Ito T.
Published: July 2002

Motivation: Protein--protein interactions are systematically examined using the yeast two-hybrid method. Consequently, a lot of protein--protein interaction data are currently being accumulated. Nevertheless, general information or knowledge on protein--protein interactions is poorly extracted from these data. Thus we have been trying to extract the knowledge from the protein--protein interaction data using data mining.

Results: A data mining method is proposed to discover association rules related to protein--protein interactions. To evaluate the detected rules by the method, a new scoring measure of the rules is introduced. The method allowed us to detect popular interaction rules such as ‘An SH3 domain binds to a proline-rich region.’ These results indicate that the method may detect novel knowledge on protein--protein interactions.

Contact: oyama@isl.intec.co.jp

* To whom correspondence should be addressed.
Black‐White Wage Inequality in the 1990s: a Decade of Progress
Authors: Couch Kenneth , Daly Mary C.
Published: July 2002

Using Current Population Survey data, we find that the gap between the wages of black and white males declined during the 1990s at a rate of about.60 percentage point per year. Wage convergence was most rapid among workers with less than 10 years of potential experience, with declines in the gap averaging 1.40 percentage points per year. Using standard decomposition methods, we find that greater occupational diversity and reductions in unobserved or residual differences are important in explaining this trend. General wage inequality tempered the rate of wage convergence between blacks and whites during the 1990s.
MCM3AP, a novel acetyltransferase that acetylates replication protein MCM3
Authors: Takei Yoshinori , Swietlik Magdalena , Tanoue Akito , Tsujimoto Gozoh , Kouzarides Tony , Laskey Ronald
Published: July 2002

The MCM proteins are essential for the initiation of DNA replication. We have isolated an MCM3‐associated protein (MCM3AP) in a two‐hybrid screen using MCM3. Here we demonstrate that MCM3AP is an acetyltransferase which acetylates MCM3 and that chromatin‐bound MCM3 is acetylated in vivo. The MCM3 acetylase, MCM3AP, is also chromatin‐bound. This study also indicates that MCM3AP contains putative acetyl CoA binding motifs conserved within the GCN5‐related N‐acetyltransferase superfamily. Mutation of those motifs significantly inhibits the MCM3 acetylase activity. Over‐expression of MCM3AP inhibits DNA replication, whereas mutation of the acetylase motifs abolishes this effect, suggesting that acetylation plays a role in DNA replication. Taken together, we suggest that MCM3 acetylation is a novel pathway which might regulate DNA replication.
A transcriptional inhibitor targeted by the atypical orphan nuclear receptor SHP
Authors: Båvner Ann , Johansson Lotta , Toresson Gudrun , Gustafsson Jan‐Åke , Treuter Eckardt
Published: July 2002

SHP (short heterodimer partner, NROB2) is an atypical orphan member of the mammalian nuclear receptor family that consists only of a putative ligand‐binding domain and thus cannot bind DNA. Instead, SHP acts as a transcriptional coregulator by inhibiting the activity of various nuclear receptors (downstream targets) via occupation of the coactivator‐binding surface and active repression. However, repression mechanisms have remained elusive and may involve coinhibitory factors (upstream targets) distinct from known nuclear receptor corepressors. Here, we describe the isolation of mouse E1A‐like inhibitor of differentiation 1 (EID1) as a candidate coinhibitor for SHP. We characterize the interactions between SHP and EID1 and identify two repression‐defective SHP mutations that have lost the ability to bind EID1. We suggest histone acetyltransferases and histones as targets for EID1 action and propose that SHP inhibition of transcription involves EID1 antagonism of CBP/p300‐dependent coactivator functions.
Pharmacodynamics of fluoroquinolones
Authors: Dalhoff A.
Published: July 2002

Fluctuating concentrations of three fluoroquinolones (moxifloxacin, sparfloxacin and ofloxacin) and a β-lactam (amoxycillin) were used in vitro to simulate antibiotic concentrations in human serum after oral doses of antibiotics. The antibiotics were tested against Staphylococcus aureus 12241 and Streptococcus pneumoniae 4241. Moxifloxacin and sparfloxacin were also tested against Escherichia coli Neumann. Human serum concentrations of moxifloxacin and ciprofloxacin were also simulated in an in-vivo murine thigh muscle model against S. aureus,S. pneumoniae and E. coli. Ciprofloxacin, sparfloxacin and ofloxacin had a dose-independent effect on Gram-positive organisms beyond their optimal dose that gave a maximum effect, as did amoxycillin. In contrast, moxifloxacin had a dose-dependent and therefore concentration-dependent effect on both Gram-positive and β-lactam-susceptible and-resistant Gram-negative organisms. The marked activity of moxifloxacin against both Gram-positive and Gram-negative organisms was confirmed in an in-vivo model. A human dose equivalent of 200 mg moxifloxacin reduced viable counts of S. pneumoniae below the limit of detection and regrowth did not occur. S. aureus was eliminated almost as effectively as S. pneumoniae. A 200 mg dose of moxifloxacin completely eliminated the original inoculum of E. coli within 6 h. Treatment of S. aureus with ciprofloxacin (250 or 500 mg) resulted in a dose-independent decrease in viable counts by approximately 3.5 log 10 cfu/mL. A 125 mg dose of ciprofloxacin almost completely eliminated the original inoculum of E. coli within 8 h, whereas both the 250 mg and 500 mg doses reduced viable counts below the limit of detection. Thus, the in-vitro and in-vivo pharmacodynamic models used in this study established that moxifloxacin was highly effective against both Gram-negative and Gram-positive bacteria.
The phytochrome family: dissection of functional roles and signalling pathways among family members
Authors: Quail Peter H.
Published: July 2002

There is considerable evidence that individual members of the five–membered phytochrome family of photoreceptors in
Arabidopsis
have differential functional roles in controlling plant photomorphogenesis. Emerging genetic evidence suggests that this differential activity may involve initially separate signalling pathway branches specific to individual family members.
Consciousness and body image: lessons from phantom limbs, Capgras syndrome and pain asymbolia
Authors:   The American Association for Research into Nervous and Mental Diseases, Ramachandran V. S.
Published: July 2002

Words such as ‘consciousness’ and ‘self’ actually encompass a number of distinct phenomena that are loosely lumped together. The study of neurological syndromes allows us to explore the neural mechanisms that might underlie different aspects of self, such as body image and emotional responses to sensory stimuli, and perhaps even laughter and humour. Mapping the ‘functional logic’ of the many different attributes of human nature on to specific neural circuits in the brain offers the best hope of understanding how the activity of neurons gives rise to conscious experience. We consider three neurological syndromes (phantom limbs, Capgras delusion and pain asymbolia) to illustrate this idea.
Neuromuscular organization of avian flight muscle: architecture of single muscle fibres in muscle units of the pectoralis (pars thoracicus) of pigeon (Columba livia)
Authors: Sokoloff A. J. , Goslow G. E.
Published: July 2002

The M. pectoralis (pars thoracicus) of pigeons (Columba livia) is comprised of short muscle fibres that do not extend from muscle origin to insertion but overlap ‘in-series’. Individual pectoralis motor units are limited in territory to a portion of muscle length and are comprised of either fast twitch, oxidative and glycolytic fibres (FOG) or fast twitch and glycolytic fibres (FG). FOG fibres make up 88 to 90% of the total muscle population and have a mean diameter one-half of that of the relatively large FG fibres. Here we report on the organization of individual fibres identified in six muscle units depleted of glycogen, three comprised of FOG fibres and three comprised of FG fibres. For each motor unit, fibre counts revealed unequal numbers of depleted fibres in different unit cross-sections. We traced individual fibres in one unit comprised of FOG fibres and a second comprised of FG fibres. Six fibres from a FOG unit (total length 15.45 mm) ranged from 10.11 to 11.82 mm in length and averaged (±s.d.) 10.74±0.79 mm. All originated bluntly (en mass) from a fascicle near the proximal end of the muscle unit and all terminated intramuscularly. Five of these ended in a taper and one ended bluntly. Fibres coursed on average for 70% of the muscle unit length. Six fibres from a FG unit (total length 34.76 mm) ranged from 8.97 to 18.38 mm in length and averaged 15.32 ±3.75 mm. All originated bluntly and terminated intramuscularly; one of these ended in a taper and five ended bluntly. Fibres coursed on average for 44% of the muscle unit length. Because fibres of individual muscle units do not extend the whole muscle unit territory, the effective cross-sectional area changes along the motor unit length. These non-uniformities in the distribution of fibres within a muscle unit emphasize that the functional interactions within and between motor units are complex.
Prospects for the clinical application of neural transplantation with the use of conditionally immortalized neuroepithelial stem cells
Authors: Gray Jeffrey A. , Hodges Helen , Sinden John
Published: July 2002

Although neural transplantation has made a relatively successful transition from the animal laboratory to human neurosurgery for the treatment of Parkinson's disease, the use of human embryonic brain tissue as the source of transplants raises difficult ethical and practical problems. These are likely to impede the widespread use of this otherwise promising therapy across the range of types of brain damage to which the results of animal experiments suggest its potential applicability. Various alternative approaches are reviewed briefly, aimed at developing sources of tissue for transplantation that can be maintainedin vitrountil needed, so obviating the requirement for fresh embryonic tissue at each occasion of surgery. Particularly promising are conditionally immortalized neuroepithelial stem cell lines in which the immortalizing gene is downregulated upon transplantation into a host brain. We describe experiments from our laboratory with the use of cells of this kind, the multipotent MHP clonal cell lines, derived from the developing hippocampus of a transgenic mouse harbouring a temperature–sensitive oncogene. Implanted into the hippocampus of rats and marmosets with damage to the CA1 cell field, the MHP36 line gave rise to healthy surviving grafts and to essentially complete recovery of cognitive function. Post–mortem study of the implanted rat brains indicated that MHP36 cells migrate to the region of damage, adopt both neuronal (pyramidal) and glial phenotypesin vivo, and reconstitute the normal laminated appearance of the CA1 cell field. We have previously shown that, when primary differentiated foetal tissue is used as the source of grafts in rats with CA1 damage, there is a stringent requirement for replacement with homotypic CA1 cells. We interpret our results as showing that the MHP36 cell line responds to putative signals associated with damage to the hippocampus and takes up a phenotype appropriate for the repair of this damage; they therefore open the way to the development of a novel strategy with widespread applicability to the treatment of the diseased or damaged human brain.
Entering the 21st century: the challenges for development
Authors: Wolfensohn James D.
Published: July 2002

By many people, the 20th century will be remembered as an era of great achievement in human endeavour, and of enormous economic growth and prosperity. Achievements in medical research, from eradicating infectious diseases to laser surgery; in engineering, from the transistor to space exploration; and in economic development have all contributed to greater well being in the world at the end of the 20th century. Among the challenges to development identified by the World Bank in the coming decades will be managing the twin processes of globalization and localization, as well as post–conflict reconstruction. These will form the backdrop of the Bank's main focus of creating a world free of poverty.
Detection and analysis of gene expression during infection by in vivo expression technology
Authors: Scott Merrell D. , Camilli Andrew
Published: July 2002

Many limitations associated with the use of
in vitro
models for study of bacterial pathogenesis can be overcome by the use of technologies that detect pathogen gene expression during the course of infection within an intact animal. in vivo expression technology (IVET) accomplishes this with versatility: it has been developed with a variety of reporter systems which allow for either in vivo selection or
ex vivo
screening. Selectable gene fusion systems generally allow for the complementation of a bacterial metabolic defect that is lethal in vivo, or for antibiotic resistance during the course of in vivo antibiotic challenge. In contrast, the screenable gene fusion system uses a site–specific DNA recombinase that, when expressed in vivo, excises a selectable gene cassette from the bacterial chromosome. Loss of this cassette can then be either screened or selected for
ex vivo
. The recombinase–based IVET can be used to detect genes that are transcriptionally induced during infection, including those expressed transiently or at low levels and, in addition, can be used to monitor the spatial and temporal expression of specific genes during the course of infection.
New concepts in fission yeast morphogenesis
Authors: Brunner Damian , Nurse Paul
Published: July 2002

The ability to generate spatial form is a fundamental characteristic of all living organisms, which has been much studied by successive generations of developmental biologists. In recent years increasing numbers of cell biologists have turned their attention to the mechanisms by which cells generate their spatial form. These include the mechanisms that position components in different places within the cell, that specify the position of these components, and that generate the overall shape of these components. These problems are entirely analogous to those studied by developmental biologists, although usually at the level of the whole organism, organ or tissue. Because the organization of all cells is basically similar, it is possible that the concepts and the underlying molecular mechanisms of cell morphogenesis may be highly conserved. In this article we consider the generation of spatial form within the fission yeast cell, focusing on emerging new concepts, which may be applicable to the morphogenesis of other cells.
Chlororespiration
Authors: Nixon Peter J.
Published: July 2002

The term ‘chlororespiration’ is used to describe the activity of a putative respiratory electron transfer chain within the thylakoid membrane of chloroplasts and was originally proposed by Bennoun in 1982 to explain effects on the redox state of the plastoquinone pool in green algae in the absence of photosynthetic electron transfer. In his original model, Bennoun suggested that the plastoquinone pool could be reduced through the action of a NAD(P)H dehydrogenase and could be oxidized by oxygen at an oxidase. At the same time an electrochemical gradient would be generated across the thylakoid membrane. This review describes the current status of the chlororespiration model in light of the recent discoveries of novel respiratory components within the chloroplast thylakoid membrane.