The Saccharomyces Genome Database (SGD, http://www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae. The SGD project provides the highest-quality manually ...curated information from peer-reviewed literature. The experimental results reported in the literature are extracted and integrated within a well-developed database. These data are combined with quality high-throughput results and provided through Locus Summary pages, a powerful query engine and rich genome browser. The acquisition, integration and retrieval of these data allow SGD to facilitate experimental design and analysis by providing an encyclopedia of the yeast genome, its chromosomal features, their functions and interactions. Public access to these data is provided to researchers and educators via web pages designed for optimal ease of use.
The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) collects and organizes biological information about the chromosomal features and gene products of the budding yeast Saccharomyces ...cerevisiae. Although published data from traditional experimental methods are the primary sources of evidence supporting Gene Ontology (GO) annotations for a gene product, high-throughput experiments and computational predictions can also provide valuable insights in the absence of an extensive body of literature. Therefore, GO annotations available at SGD now include high-throughput data as well as computational predictions provided by the GO Annotation Project (GOA UniProt; http://www.ebi.ac.uk/GOA/). Because the annotation method used to assign GO annotations varies by data source, GO resources at SGD have been modified to distinguish data sources and annotation methods. In addition to providing information for genes that have not been experimentally characterized, GO annotations from independent sources can be compared to those made by SGD to help keep the literature-based GO annotations current.
Accurate guidance of an ablation catheter is critical in the RF ablation (RFA) of ventricular tachycardia (VT). With current technologies, it is challenging to rapidly and accurately localize the ...site of origin of an arrhythmia, often restricting treatment to patients with hemodynamically stable arrhythmias. We investigated the effectiveness of a new guidance method, the inverse solution guidance algorithm (ISGA), which is based on a single-equivalent dipole representation of cardiac electrical activity and is suitable for patients with hemodynamically unstable VT. Imaging was performed in homogeneous and inhomogeneous saline-filled torso phantoms in which a catheter tip was guided toward a stationary electrical dipole source over distances of more than 5 cm. Using ISGA, the moving catheter tip was guided to within 0.61 plusmn0.43 and 0.55 plusmn0.39 mm of the stationary source in the homogeneous and inhomogeneous phantoms, respectively. This accuracy was achieved with less than ten movements of the catheter. These results suggest that ISGA has potential to provide accurate and efficient guidance for RFA procedures in the patient population with hemodynamically unstable arrhythmias.
► We examine whether the Washington State Achiever program increases college plans and attainment. ► We use a quasi-experimental design based on pre- and post-intervention surveys of high school ...seniors. ► We find a (significant) net positive program effect on 4-year college attendance. ► The magnitude of the program effect is uneven across school contexts.
The Washington State Achiever (WSA) program was a large-scale educational intervention of scholarships, mentoring, and school redesign designed to encourage students from moderate and low income families to attend college in Washington State. Using a quasi-experimental design based on pre- and post-intervention surveys of high school seniors in program and non-program schools, we find a significant WSA effect on educational outcomes, net of the demographic and socioeconomic composition of students across schools. Across the three intervention high schools, the program is strongly significant in one school, significant after a lag in another school, and not significant in a third. We speculate about the potential reasons for the differential program effect across high schools.
The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are ...freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.
The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is a scientific database for the molecular biology and genetics of the yeast Saccharomyces cerevisiae, which is commonly known as ...baker's or budding yeast. The information in SGD includes functional annotations, mapping and sequence information, protein domains and structure, expression data, mutant phenotypes, physical and genetic interactions and the primary literature from which these data are derived. Here we describe how published phenotypes and genetic interaction data are annotated and displayed in SGD.
Increasingly, we are aware as a community of the growing need to manage the avalanche of genomic and metagenomic data, in addition to related data types like ribosomal RNA and barcode sequences, in a ...way that tightly integrates contextual data with traditional literature in a machine-readable way. It is for this reason that the Genomic Standards Consortium (GSC) formed in 2005. Here we suggest that we move beyond the development of standards and tackle standards compliance and improved data capture at the level of the scientific publication. We are supported in this goal by the fact that the scientific community is in the midst of a publishing revolution. This revolution is marked by a growing shift away from a traditional dichotomy between "journal articles" and "database entries" and an increasing adoption of hybrid models of collecting and disseminating scientific information. With respect to genomes and metagenomes and related data types, we feel the scientific community would be best served by the immediate launch of a central repository of short, highly structured "Genome Notes" that must be standards compliant. This could be done in the context of an existing journal, but we also suggest the more radical solution of launching a new journal. Such a journal could be designed to cater to a wide range of standards-related content types that are not currently centralized in the published literature. It could also support the demand for centralizing aspects of the "gray literature" (documents developed by institutions or communities) such as the call by the GSC for a central repository of Standard Operating Procedures describing the genomic annotation pipelines of the major sequencing centers. We argue that such an "eJournal," published under the Open Access paradigm by the GSC, could be an attractive publishing forum for a broader range of standardization initiatives within, and beyond, the GSC and thereby fill an unoccupied yet increasingly important niche within the current research landscape.
Clenbuterol treatment for several weeks prevented up to one-third of the reduction in mineralization of femurs and tibias caused by sectioning of the sciatic nerve in young rats. The normalizing ...effect of clenbuterol on bone mineral content was directly proportional to similar alterations in muscle mass, which in turn could be abolished by ablation of the triceps surae or hindlimb unweighting and reduced by hypophysectomy. In contrast to the effects of inactivity, ovariectomy caused small reductions (2-4%) in bone density that were not affected by clenbuterol and were not accompanied by changes in ash weight. Together, our results suggest that the ability of beta 2-agonists to retard the loss in net muscle mass and enhance contractile tension can oppose net bone loss caused by denervation. Increases in contractile tension caused by beta 2-agonists may enhance the utility of exercise or electrical stimulation as countermeasures for the effects of scoliosis, prolonged bed rest, spinal cord injury, or weightlessness in space on bone mass.
We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs, and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a ...1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high-throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available at https://clue.io.
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•A new gene expression profiling method, L1000, dramatically lowers cost•The Connectivity Map now includes 1.3 million publicly accessible L1000 profiles•Facilitates discovery of small-molecule mechanism and annotation of genetic variants•The work establishes feasibility and utility of a truly comprehensive Connectivity Map
The next generation Connectivity Map, a large-scale compendium of functional perturbations in cultured human cells coupled to a gene-expression readout, facilitates the discovery of connections between genes, drugs, and diseases.
Product R (Reticulose™) is a peptide–nucleic acid immunomodulator recently shown to enhance the expression of mRNAs encoding pro-inflammatory cytokines. Interleukin 8 (IL-8) and macrophage ...chemoattractant protein-1 (MCP-1) are pro-inflammatory chemokines involved in immune cell mobilization and stimulation. To determine whether Product R acts by upregulating these chemokines, we assayed its effects on the expression of IL-8 and MCP-1 mRNAs and proteins by human monocytic U937 cells and by adherent peripheral blood mononuclear cells (PBMCs). U937 cells were cultured for 0–21 days in media containing 0–20% Product R or phosphate-buffered saline (PBS). Compared to control cultures, cells cultured in Product R expressed increased amounts of IL-8 and MCP-1 mRNAs, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Product R also increased secretion of IL-8 and MCP-1, as measured by enzyme-linked immunosorbent assay (ELISA), and boosted secretion induced by bacterial lipopolysaccharide (LPS), in a time- and dose-dependent manner. In adherent PBMCs, Product R increased IL-8 and MCP-1 secretion, but reduced LPS-induced MCP-1 secretion. While mRNAs encoding the IL-8 receptor, CXCR2, and the MCP-1 receptor, CCR2, were increased in U937 cells cultured in 5–10% Product R, we observed no change in binding of receptor-specific antibodies. These findings suggest that Product R upregulates the expression of IL-8 and MCP-1, which may boost immune system activity in virally-infected patients.
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