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Susan J Brown

Publications and source records attributed to Susan J Brown.

At least 19 recordsLinked to original sources
PubMed2006

BeetleBase: the model organism database for Tribolium castaneum.

BeetleBase (http://www.bioinformatics.ksu.edu/BeetleBase/) is an integrated resource for the Tribolium research community. The red flour beetle (Tribolium castaneum) is an important model organism for genetics, developmental biology, toxicology and comparative genomics, the genome of which has recently been sequenced. BeetleBase is constructed to integrate the genomic sequence data with information about genes, mutants, genetic markers, expressed sequence tags and publications. BeetleBase uses the Chado data model and software components developed by the Generic Model Organism Database (GMOD) project. This strategy not only reduces the time required to develop the database query tools but also makes the data structure of BeetleBase compatible with that of other model organism databases. BeetleBase will be useful to the Tribolium research community for genome annotation as well as comparative genomics.

Animals↗
PubMed2006

Patterns of conservation and change in honey bee developmental genes.

The current insect genome sequencing projects provide an opportunity to extend studies of the evolution of developmental genes and pathways in insects. In this paper we examine the conservation and divergence of genes and developmental processes between Drosophila and the honey bee; two holometabolous insects whose lineages separated approximately 300 million years ago, by comparing the presence or absence of 308 Drosophila developmental genes in the honey bee. Through examination of the presence or absence of genes involved in conserved pathways (cell signaling, axis formation, segmentation and homeobox transcription factors), we find that the vast majority of genes are conserved. Some genes involved in these processes are, however, missing in the honey bee. We have also examined the orthology of Drosophila genes involved in processes that differ between the honey bee and Drosophila. Many of these genes are preserved in the honey bee despite the process in which they act in Drosophila being different or absent in the honey bee. Many of the missing genes in both situations appear to have arisen recently in the Drosophila lineage, have single known functions in Drosophila, and act early in developmental pathways, while those that are preserved have pleiotropic functions. An evolutionary interpretation of these data is that either genes with multiple functions in a common ancestor are more likely to be preserved in both insect lineages, or genes that are preserved throughout evolution are more likely to co-opt additional functions.

Amino Acid Sequence↗
PubMed2006

Evolutionary flexibility of pair-rule patterning revealed by functional analysis of secondary pair-rule genes, paired and sloppy-paired in the short-germ insect, Tribolium castaneum.

In the Drosophila segmentation hierarchy, periodic expression of pair-rule genes translates gradients of regional information from maternal and gap genes into the segmental expression of segment polarity genes. In Tribolium, homologs of almost all the eight canonical Drosophila pair-rule genes are expressed in pair-rule domains, but only five have pair-rule functions. even-skipped, runt and odd-skipped act as primary pair-rule genes, while the functions of paired (prd) and sloppy-paired (slp) are secondary. Since secondary pair-rule genes directly regulate segment polarity genes in Drosophila, we analyzed Tc-prd and Tc-slp to determine the extent to which this paradigm is conserved in Tribolium. We found that the role of prd is conserved between Drosophila and Tribolium; it is required in both insects to activate engrailed in odd-numbered parasegments and wingless (wg) in even-numbered parasegments. Similarly, slp is required to activate wg in alternate parasegments and to maintain the remaining wg stripes in both insects. However, the parasegmental register for Tc-slp is opposite that of Drosophila slp1. Thus, while prd is functionally conserved, the fact that the register of slp function has evolved differently in the lineages leading to Drosophila and Tribolium reveals an unprecedented flexibility in pair-rule patterning.

Amino Acid Sequence↗
PubMed2006

The Tribolium castaneum ortholog of Sex combs reduced controls dorsal ridge development.

In insects, the boundary between the embryonic head and thorax is formed by the dorsal ridge, a fused structure composed of portions of the maxillary and labial segments. However, the mechanisms that promote development of this unusual structure remain a mystery. In Drosophila, mutations in the Hox genes Sex combs reduced and Deformed have been reported to cause abnormal dorsal ridge formation, but the significance of these abnormalities is not clear. We have identified three mutant allele classes of Cephalothorax, the Tribolium castaneum (red flour beetle) ortholog of Sex combs reduced, each of which has a different effect on dorsal ridge development. By using Engrailed expression to monitor dorsal ridge development in these mutants, we demonstrate that Cephalothorax promotes the fusion and subsequent dorsolateral extension of the maxillary and labial Engrailed stripes (posterior compartments) during dorsal ridge formation. Molecular and genetic analysis of these alleles indicates that the N terminus of Cephalothorax is important for the fusion step, but is dispensable for Engrailed stripe extension. Thus, we find that specific regions of Cephalothorax are required for discrete steps in dorsal ridge formation.

Alleles↗
PubMed2006

BindN: a web-based tool for efficient prediction of DNA and RNA binding sites in amino acid sequences.

BindN (http://bioinformatics.ksu.edu/bindn/) takes an amino acid sequence as input and predicts potential DNA or RNA-binding residues with support vector machines (SVMs). Protein datasets with known DNA or RNA-binding residues were selected from the Protein Data Bank (PDB), and SVM models were constructed using data instances encoded with three sequence features, including the side chain pK(a) value, hydrophobicity index and molecular mass of an amino acid. The results suggest that DNA-binding residues can be predicted at 69.40% sensitivity and 70.47% specificity, while prediction of RNA-binding residues achieves 66.28% sensitivity and 69.84% specificity. When compared with previous studies, the SVM models appear to be more accurate and more efficient for online predictions. BindN provides a useful tool for understanding the function of DNA and RNA-binding proteins based on primary sequence data.

Amino Acids↗
PubMed2006

A pair-rule gene circuit defines segments sequentially in the short-germ insect Tribolium castaneum.

In Drosophila, a hierarchy of maternal, gap, pair-rule, and segment polarity gene interactions regulates virtually simultaneous blastoderm segmentation. For the last decade, studies have focused on revealing the extent to which Drosophila segmentation mechanisms are conserved in other arthropods where segments are added sequentially from anterior to posterior in a cellular environment. Despite our increased knowledge of individual segmentation genes, details of their interactions in non-Drosophilid insects are not well understood. We analyzed the Tribolium orthologs of Drosophila pair-rule genes, which display pair-rule expression patterns. Tribolium castaneum paired (Tc-prd) and sloppy-paired (Tc-slp) genes produced pair-rule phenotypes when their transcripts were severely reduced by RNA interference. In contrast, similar analysis of T. castaneum even-skipped (Tc-eve), runt (Tc-run), or odd-skipped (Tc-odd) genes produced severely truncated, almost completely asegmental phenotypes. Analysis of interactions between pair-rule components revealed that Tc-eve, Tc-run, and Tc-odd form a three-gene circuit to regulate one another as well as their downstream targets, Tc-prd and Tc-slp. The complement of primary pair-rule genes in Tribolium differs from Drosophila in that it includes Tc-odd but not Tc-hairy. This gene circuit defines segments sequentially in double segment periodicity. Furthermore, this single mechanism functions in the early blastoderm stage and subsequently during germ-band elongation. The periodicity of the Tribolium pair-rule gene interactions reveals components of the genetic hierarchy that are regulated in a repetitive circuit or clock-like mechanism. This pair-rule gene circuit provides insight into short-germ segmentation in Tribolium that may be more generally applicable to segmentation in other arthropods.

Animals↗
PubMed2006

Rheumatology telephone helplines: patient and health professionals' requirements.

OBJECTIVES: The aim of this study was to ascertain patients' and health professionals' requirements from a rheumatology helpline and how such a service should be delivered. METHODS: Self-completed questionnaires were administered to both users of rheumatology helplines, patients and health professionals (HPs), and providers of rheumatology services at five UK NHS trusts. Additional data were sought from experts in the field. Information was elicited on access to the service, preferred waiting time for response to a call, acceptability of an answerphone and choice of HP responding. Quantitative data were analysed using percentages and Chi-squared tests. Open questions were analysed as free text responses, and organized into clusters of themes. RESULTS: A total of 607 questionnaires were returned, 523 from users (411 patients, 112 health professionals) and 84 from providers. There were no significant differences across the five Trusts. The top six reasons for patients contacting the helpline were: advice on changes in condition, drug information, understanding symptoms, blood results, information on diagnosis, and appointment queries. All groups recommended a return call on the same day and were happy to leave an answerphone message. HP users requested additional access via e-mail and fax. Rheumatology practitioners were deemed the most appropriate personnel to staff a helpline. CONCLUSIONS: The findings of this study have contributed a valuable insight into the essential components of a rheumatology helpline service from a user and provider perspective. These data will add to existing recommendations for the management of a rheumatology helpline service and ultimately contribute to a proposal for national guidelines.

Adult↗
PubMed2005

Genetic linkage maps of the red flour beetle, Tribolium castaneum, based on bacterial artificial chromosomes and expressed sequence tags.

A genetic linkage map was constructed in a backcross family of the red flour beetle, Tribolium castaneum, based largely on sequences from bacterial artificial chromosome (BAC) ends and untranslated regions from random cDNA's. In most cases, dimorphisms were detected using heteroduplex or single-strand conformational polymorphism analysis after specific PCR amplification. The map incorporates a total of 424 markers, including 190 BACs and 165 cDNA's, as well as 69 genes, transposon insertion sites, sequence-tagged sites, microsatellites, and amplified fragment-length polymorphisms. Mapped loci are distributed along 571 cM, spanning all 10 linkage groups at an average marker separation of 1.3 cM. This genetic map provides a framework for positional cloning and a scaffold for integration of the emerging physical map and genome sequence assembly. The map and corresponding sequences can be accessed through BeetleBase (http://www.bioinformatics.ksu.edu/BeetleBase/).

Animals↗
PubMed2005

Computationally analyzing the possible biological function of YJL103C--an ORF potentially involved in the regulation of energy process in yeast.

Although the complete genomes of a number of organisms have been sequenced, the biological functions of many genes are still not known. Because experimentally studying the functions of those genes one by one requires tremendous time, it is vital to use published resources like microarray gene expression data for computational analysis of gene functions. One example is YJL103C, a yeast gene of unknown function in the Saccharomyces Genome Database (SGD). It is possible to quickly infer its biological function by computational analysis. In this study, we present an efficient model to explore the biological function of a novel gene using microarray data. We showed that the expression pattern of YJL103C is most similar to the genes in the energy group and respiratory chain subgroup. We further found that YJL103C contains a HAP2,3,4 box in its promoter region and a cytochrome C heme-binding signature in its protein sequence. Our findings define a potential role for YJL103C in the regulation of energy metabolism, specifically in the process of oxidative phosphorylation. Similar bioinformatics methods can be applied to infer the biological functions of other novel genes in organisms for which microarray data are available. In this work, we selected a single gene of unknown function as a case study. By focusing on the power of computer analysis and bioinformatics on the available microarray data, we have determined the likely biological function of YJL103C. Our study provides a method by which to explore the potential function of other genes currently annotated as having an unknown function in any organism for which global gene expression data are available.

Binding Sites↗
PubMed2004

Incremental genetic K-means algorithm and its application in gene expression data analysis.

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.

Algorithms↗
PubMed2004

Computational identification of novel chitinase-like proteins in the Drosophila melanogaster genome.

MOTIVATION: Multiple chitinases as well as lectins closely related to them have been characterized previously from many insect species and the corresponding genes/cDNAs have been cloned. However, the identification of the entire assortment of genes for chitinase family proteins and their differences in biochemical properties have not been carried out in any individual insect species. The completion of the entire DNA sequence of Drosophila melanogaster (fruit fly) genome and identification of open reading frames presents an opportunity to study the structures and functions of chitinase-like proteins, and also to identify new members of this family in Drosophila. We are, therefore, interested in studying the functional genomics of chitinase-like gene families in insects. METHODS: We searched the Drosophila protein sequences database using fully characterized insect chitinase sequences and BLASTP software, identified all the putative chitinase-like proteins encoded in Drosophila genome, and predicted their structures using domain analysis tools. A phylogenetic analysis of the chitinase-like proteins from Drosophila and several other insect species was carried out. The structures of these chitinases were modeled using homology modeling software. RESULTS: Our analysis revealed the presence of 18 chitinase-like proteins in the Drosophila protein database. Among these are seven novel chitinase-like proteins that contain four signature amino acid sequences of chitinases belonging to family 18 glycosylhydrolases, including both acidic and hydrophobic amino acid residues critical for enzyme activity. All the proteins contain at least one catalytic domain with one having four catalytic domains. Phylogenetic analysis of chitinase-like proteins from Drosophila and other insects revealed an evolutionary relationship among all these proteins, which indicated gene duplication and domain shuffling to generate the observed diversity in the encoded proteins. Homology modeling showed that all the Drosophila chitinase-like proteins contain one or more catalytic domains with a (alpha/beta)8 barrel-like structure. Our results suggest that insects utilize multiple family 18 chitinolytic enzymes and also non-enzymatic chitinase-like proteins for degrading/remodeling/binding to chitin in different insect anatomical extracellular structures, such as the cuticle, peritrophic membrane, trachea and mouth parts during insect development, and possibly for other roles including chitin synthesis. AVAILABILITY: Perl program and supplementary material are available at http://www.ksu.edu/bioinformatics/supplementary.htm

Amino Acid Sequence↗
PubMed2004

The impact of group education on participants' management of their disease in lupus and scleroderma.

OBJECTIVES: The aim of this study was to investigate the impact of the pilot education programmes, entitled 'Focus on Lupus' and 'Focus on Scleroderma', upon participants' management of their disease. METHODS: Five people with lupus and five with scleroderma were invited to take part in individual semi-structured interviews. Qualitative analysis of transcripts was performed using a framework approach. Views relating to changes in knowledge and behaviour, increased empowerment, meeting others and the format and delivery of the programmes were explored. RESULTS: Analysis of the interviews revealed overall satisfaction with both programmes, however people with lupus had more positive feelings about their attendance. Both disease groups considered it valuable to meet others with the same disease and welcomed the involvement of a patient educator within the programme planning team. The main difference between the two groups concerned behaviour change. The lupus group revealed more definite life changes. Participants unanimously regarded the format of the programme highly and most were satisfied with the content.

Journal Article↗
PubMed2003

Beetling around the genome.

The red flour beetle, Tribolium castaneum, has been selected for whole genome shotgun sequencing in the next year. In this minireview, we discuss some of the genetic and genomic tools and biological properties of Tribolium that have established its importance as an organism for agricultural and biomedical research as well as for studies of development and evolution. A Tribolium genomic database, Beetlebase, is being constructed to integrate genetic, genomic and biological data as it becomes available.

Animals↗
PubMed2003

The expression and function of the achaete-scute genes in Tribolium castaneum reveals conservation and variation in neural pattern formation and cell fate specification.

The study of achaete-scute (ac/sc) genes has recently become a paradigm to understand the evolution and development of the arthropod nervous system. We describe the identification and characterization of the ac/sc genes in the coleopteran insect species Tribolium castaneum. We have identified two Tribolium ac/sc genes - achaete-scute homolog (Tc-ASH) a proneural gene and asense (Tc-ase) a neural precursor gene that reside in a gene complex. Focusing on the embryonic central nervous system we find that Tc-ASH is expressed in all neural precursors and the proneural clusters from which they segregate. Through RNAi and misexpression studies we show that Tc-ASH is necessary for neural precursor formation in Tribolium and sufficient for neural precursor formation in Drosophila. Comparison of the function of the Drosophila and Tribolium proneural ac/sc genes suggests that in the Drosophila lineage these genes have maintained their ancestral function in neural precursor formation and have acquired a new role in the fate specification of individual neural precursors. Furthermore, we find that Tc-ase is expressed in all neural precursors suggesting an important and conserved role for asense genes in insect nervous system development. Our analysis of the Tribolium ac/sc genes indicates significant plasticity in gene number, expression and function, and implicates these modifications in the evolution of arthropod neural development.

Amino Acid Sequence↗
PubMed2002

Tribolium Hox genes repress antennal development in the gnathos and trunk.

Evidence from Drosophila suggests that Hox genes not only specify regional identity, but have the additional function of repressing antennal development within their normal domains. This is dramatically demonstrated by a series of Hox mutants in the red flour beetle, Tribolium castaneum, and is likely an ancient function of Hox genes in insects.

Animals↗
PubMed2002

Cloning and characterization of the Tribolium castaneum eye-color genes encoding tryptophan oxygenase and kynurenine 3-monooxygenase.

The use of eye-color mutants and their corresponding genes as scorable marker systems has facilitated the development of transformation technology in Drosophila and other insects. In the red flour beetle, Tribolium castaneum, the only currently available system for germline transformation employs the exogenous marker gene, EGFP, driven by an eye-specific promoter. To exploit the advantages offered by eye-pigmentation markers, we decided to develop a transformant selection system for Tribolium on the basis of mutant rescue. The Tribolium orthologs of the Drosophila eye-color genes vermilion (tryptophan oxygenase) and cinnabar (kynurenine 3-monooxygenase) were cloned and characterized. Conceptual translations of Tc vermilion (Tcv) and Tc cinnabar (Tccn) are 71 and 51% identical to their respective Drosophila orthologs. We used RNA interference (RNAi) to show that T. castaneum larvae lacking functional Tcv or Tccn gene products also lack the pigmented eyespots observed in wild-type larvae. Five available eye-color mutations were tested for linkage to Tcv or Tccn via recombinational mapping. No linkage was found between candidate mutations and Tccn. However, tight linkage was found between Tcv and the white-eye mutation white, here renamed vermilion(white) (v(w)). Molecular analysis indicates that 80% of the Tcv coding region is deleted in v(w) beetles. These observations suggest that the Tribolium eye is pigmented only by ommochromes, not pteridines, and indicate that Tcv is potentially useful as a germline transformation marker.

Animals↗
PubMed2002

Sequence of the Tribolium castaneum homeotic complex: the region corresponding to the Drosophila melanogaster antennapedia complex.

The homeotic selector genes of the red flour beetle, Tribolium castaneum, are located in a single cluster. We have sequenced the region containing the homeotic selector genes required for proper development of the head and anterior thorax, which is the counterpart of the ANTC in Drosophila. This 280-kb interval contains eight homeodomain-encoding genes, including single orthologs of the Drosophila genes labial, proboscipedia, Deformed, Sex combs reduced, fushi tarazu, and Antennapedia, as well as two orthologs of zerknüllt. These genes are all oriented in the same direction, as are the Hox genes of amphioxus, mice, and humans. Although each transcription unit is similar to its Drosophila counterpart in size, the Tribolium genes contain fewer introns (with the exception of the two zerknüllt genes), produce shorter mRNAs, and encode smaller proteins. Unlike the ANTC, this region of the Tribolium HOMC contains no additional genes.

Amino Acid Sequence↗