14 research outputs found

    Crowdsourcing biocuration: The Community Assessment of Community Annotation with Ontologies (CACAO).

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    Experimental data about gene functions curated from the primary literature have enormous value for research scientists in understanding biology. Using the Gene Ontology (GO), manual curation by experts has provided an important resource for studying gene function, especially within model organisms. Unprecedented expansion of the scientific literature and validation of the predicted proteins have increased both data value and the challenges of keeping pace. Capturing literature-based functional annotations is limited by the ability of biocurators to handle the massive and rapidly growing scientific literature. Within the community-oriented wiki framework for GO annotation called the Gene Ontology Normal Usage Tracking System (GONUTS), we describe an approach to expand biocuration through crowdsourcing with undergraduates. This multiplies the number of high-quality annotations in international databases, enriches our coverage of the literature on normal gene function, and pushes the field in new directions. From an intercollegiate competition judged by experienced biocurators, Community Assessment of Community Annotation with Ontologies (CACAO), we have contributed nearly 5,000 literature-based annotations. Many of those annotations are to organisms not currently well-represented within GO. Over a 10-year history, our community contributors have spurred changes to the ontology not traditionally covered by professional biocurators. The CACAO principle of relying on community members to participate in and shape the future of biocuration in GO is a powerful and scalable model used to promote the scientific enterprise. It also provides undergraduate students with a unique and enriching introduction to critical reading of primary literature and acquisition of marketable skills

    Genomic diversity of bacteriophages infecting Microbacterium spp

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    The bacteriophage population is vast, dynamic, old, and genetically diverse. The genomics of phages that infect bacterial hosts in the phylum Actinobacteria show them to not only be diverse but also pervasively mosaic, and replete with genes of unknown function. To further explore this broad group of bacteriophages, we describe here the isolation and genomic characterization of 116 phages that infect Microbacterium spp. Most of the phages are lytic, and can be grouped into twelve clusters according to their overall relatedness; seven of the phages are singletons with no close relatives. Genome sizes vary from 17.3 kbp to 97.7 kbp, and their G+C% content ranges from 51.4% to 71.4%, compared to ~67% for their Microbacterium hosts. The phages were isolated on five different Microbacterium species, but typically do not efficiently infect strains beyond the one on which they were isolated. These Microbacterium phages contain many novel features, including very large viral genes (13.5 kbp) and unusual fusions of structural proteins, including a fusion of VIP2 toxin and a MuF-like protein into a single gene. These phages and their genetic components such as integration systems, recombineering tools, and phage-mediated delivery systems, will be useful resources for advancing Microbacterium genetics

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    The next generation of synthetic cannabinoids : detection, activity, and potential toxicity of pent-4en and but-3en analogues including MDMB-4en-PINACA

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    A new class of synthetic cannabinoids has emerged as new psychoactive substances (NPS). Similar in structure to JWH-022, these substances contain alkene modifications to the tail region of the synthetic cannabinoid core structure, and nomenclature denotes these new analogues as pent-4en or but-3en species. Internationally, two analogues from this new series recently emerged: MDMB-4en-PINACA and MMB-4en-PICA. Previously, data regarding activity and potential toxicity were not available.In vitroassessment of cannabinoid receptor 1 (CB1) activation via the beta-arrestin 2 recruitment was studied for three (3) pent-4en analogues, one (1) but-3en analogue, and one (1) principal metabolite. MDMB-4en-PINACA (2.47 nM, 239%), MDMB-4en-PICA (11.5 nM, 302%), and MDMB-3en-BINACA (14.3 nM, 286%) were highly potent and efficacious (comparison: JWH-018, 25.3 nM, 100%), while the potencies of MMB-4en-PICA and MDMB-4en-PINACA 3,3-dimethylbutanoic acid were markedly lower. Modifications to core and tail structural features (i.e., indole vs. indazole) led to relatively small differences in potency, while changes among the head region led to larger differences. Sample-mining and data-mining conducted on toxicology samples led to the identification of MDMB-4en-PINACA in 25 forensic toxicology cases, including postmortem and impaired driving investigations, with case details and limited histories described herein. Moderate geographical distribution of MDMB-4en-PINACA was noted in the United States with emergence in the Northeast, Midwest, South, and West regions. Results from toxicology testing paired with case history show the potential for MDMB-4en-PINACA to cause or contribute to impairment or death. Forensic scientists, public health and public safety officials, law enforcement, clinicians, medical examiners, and coroners should consider involvement of emergent synthetic cannabinoids in their work and that new analogues containing an alkene tail can retain similar or increased potency and toxicity
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