Caenorhabditis elegans Gα_q Regulates Egg-Laying Behavior via a PLCβ-Independent and Serotonin-Dependent Signaling Pathway and Likely Functions Both in the Nervous System and in Muscle

egl-30 encodes the single C. elegans ortholog of vertebrate Gα_q family members. We analyzed the expression pattern of EGL-30 and found that it is broadly expressed, with highest expression in the nervous system and in pharyngeal muscle. We isolated dominant, gain-of-function alleles of egl-30 as intragenic revertants of an egl-30reduction-of-function mutation. Using these gain-of-function mutants and existing reduction-of-function mutants, we examined the site and mode of action of EGL-30. On the basis of pharmacological analysis, it has been determined that egl-30 functions both in the nervous system and in the vulval muscles for egg-laying behavior. Genetic epistasis over mutations that eliminate detectable levels of serotonin reveals that egl-30requires serotonin to regulate egg laying. Furthermore, pharmacological response assays strongly suggest that EGL-30 may directly couple to a serotonin receptor to mediate egg laying. We also examined genetic interactions with mutations in the gene that encodes the single C. elegans homolog of PLCβ and mutations in genes that encode signaling molecules downstream of PLCβ. We conclude that PLCβ functions in parallel with egl-30 with respect to egg laying or is not the major effector of EGL-30. In contrast, PLCβ-mediated signaling is likely downstream of EGL-30 with respect to pharyngeal-pumping behavior. Our data indicate that there are multiple signaling pathways downstream of EGL-30 and that different pathways could predominate with respect to the regulation of different behaviors

Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community

Background: Caenorhabditis elegans gene-based phenotype information dates back to the 1970’s, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results: We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO). The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions: We provide a phenotype ontology (WPO) that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and interoperability across the different Model Organism Databases (MODs) and other biological databases. This standardized phenotype ontology will therefore allow for more complex data queries and enhance bioinformatic analyses

Caenorhabditis elegans Gα_q Regulates Egg-Laying Behavior via a PLCβ-Independent and Serotonin-Dependent Signaling Pathway and Likely Functions Both in the Nervous System and in Muscle

egl-30 encodes the single C. elegans ortholog of vertebrate Gα_q family members. We analyzed the expression pattern of EGL-30 and found that it is broadly expressed, with highest expression in the nervous system and in pharyngeal muscle. We isolated dominant, gain-of-function alleles of egl-30 as intragenic revertants of an egl-30reduction-of-function mutation. Using these gain-of-function mutants and existing reduction-of-function mutants, we examined the site and mode of action of EGL-30. On the basis of pharmacological analysis, it has been determined that egl-30 functions both in the nervous system and in the vulval muscles for egg-laying behavior. Genetic epistasis over mutations that eliminate detectable levels of serotonin reveals that egl-30requires serotonin to regulate egg laying. Furthermore, pharmacological response assays strongly suggest that EGL-30 may directly couple to a serotonin receptor to mediate egg laying. We also examined genetic interactions with mutations in the gene that encodes the single C. elegans homolog of PLCβ and mutations in genes that encode signaling molecules downstream of PLCβ. We conclude that PLCβ functions in parallel with egl-30 with respect to egg laying or is not the major effector of EGL-30. In contrast, PLCβ-mediated signaling is likely downstream of EGL-30 with respect to pharyngeal-pumping behavior. Our data indicate that there are multiple signaling pathways downstream of EGL-30 and that different pathways could predominate with respect to the regulation of different behaviors

Dyslexia-friendly schools and parent partnership: inclusion and home-school relationships

This is a postprint of an article whose final and definitive form has been published in the European Journal of Special Needs Education© 2005 Copyright Taylor & Francis; European Journal of Special Needs Education is available online at http://www.informaworld.comThis paper summarizes an action research project in five local areas in the south-west of England which aimed to support parents of children with dyslexic difficulties who were experiencing problems in obtaining appropriate provision in mainstream schools. It was based on the importance of effective parental partnership and quality inclusive practice for children having dyslexic difficulties. A development officer worked over two years in the five participating LEAs that were selected to represent a range of professional practice with a mix of urban and rural populations. As part of the evaluation, the authors also examined longitudinally the educational experiences of a sample of parents. The paper includes a conceptual framework of parental agency in this field in terms of knowledge, identity and parental strategies, and the conditions under which parents escalate their strategies to secure appropriate provision for their children. The support provided by the development officer is analysed in terms of the kinds of support requests received, the kinds of support offered and qualitative evidence of the impact of this support. This research is theorized in terms of current ideas about parent-partnership and theories about parent-teacher relations in terms of the diversity of parents. It highlights the significance of thinking about inclusive schooling and parent-school relations in terms of the interconnections between general systems for all, for those with special educational needs and those with specific difficulties. The policy and practice implications are interpreted in terms of the importance of a system of extended professionalism, which is inclusive of parents with learning difficulties and disabilities.The research project this paper summarises was funded by the British Dyslexia Association (BDA) and the Buttle Trust

WormBase: a multi-species resource for nematode biology and genomics

WormBase (http://www.wormbase.org/) is the central data repository for information about Caenorhabditis elegans and related nematodes. As a model organism database, WormBase extends beyond the genomic sequence, integrating experimental results with extensively annotated views of the genome. The WormBase Consortium continues to expand the biological scope and utility of WormBase with the inclusion of large-scale genomic analyses, through active data and literature curation, through new analysis and visualization tools, and through refinement of the user interface. Over the past year, the nearly complete genomic sequence and comparative analyses of the closely related species Caenorhabditis briggsae have been integrated into WormBase, including gene predictions, ortholog assignments and a new synteny viewer to display the relationships between the two species. Extensive site-wide refinement of the user interface now provides quick access to the most frequently accessed resources and a consistent browsing experience across the site. Unified single-page views now provide complete summaries of commonly accessed entries like genes. These advances continue to increase the utility of WormBase for C.elegans researchers, as well as for those researchers exploring problems in functional and comparative genomics in the context of a powerful genetic system

WormBase: a comprehensive data resource for Caenorhabditis biology and genomics

WormBase (http://www.wormbase.org), the model organism database for information about Caenorhabditis elegans and related nematodes, continues to expand in breadth and depth. Over the past year, WormBase has added multiple large-scale datasets including SAGE, interactome, 3D protein structure datasets and NCBI KOGs. To accommodate this growth, the International WormBase Consortium has improved the user interface by adding new features to aid in navigation, visualization of large-scale datasets, advanced searching and data mining. Internally, we have restructured the database models to rationalize the representation of genes and to prepare the system to accept the genome sequences of three additional Caenorhabditis species over the coming year

WormBase: better software, richer content

WormBase (), the public database for genomics and biology of Caenorhabditis elegans, has been restructured for stronger performance and expanded for richer biological content. Performance was improved by accelerating the loading of central data pages such as the omnibus Gene page, by rationalizing internal data structures and software for greater portability, and by making the Genome Browser highly customizable in how it views and exports genomic subsequences. Arbitrarily complex, user-specified queries are now possible through Textpresso (for all available literature) and through WormMart (for most genomic data). Biological content was enriched by reconciling all available cDNA and expressed sequence tag data with gene predictions, clarifying single nucleotide polymorphism and RNAi sites, and summarizing known functions for most genes studied in this organism

WormBase: new content and better access

WormBase (), a model organism database for Caenorhabditis elegans and other related nematodes, continues to evolve and expand. Over the past year WormBase has added new data on C.elegans, including data on classical genetics, cell biology and functional genomics; expanded the annotation of closely related nematodes with a new genome browser for Caenorhabditis remanei; and deployed new hardware for stronger performance. Several existing datasets including phenotype descriptions and RNAi experiments have seen a large increase in new content. New datasets such as the C.remanei draft assembly and annotations, the Vancouver Fosmid library and TEC-RED 5′ end sites are now available as well. Access to and searching WormBase has become more dependable and flexible via multiple mirror sites and indexing through Google

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues