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    Date Issued2016 (1)2015 (1)Author
    Hof, Patrick R. (2)
    Akbarian, Schahram (1)Bandrowski, Anita (1)Brush, Matthew (1)Croxson, Paula L. (1)View MoreUMass Chan AffiliationDepartment of Psychiatry (1)Department of Radiology, Division of Translational Anatomy (1)Document TypeJournal Article (2)KeywordAntipsychotic (1)Clozapine (1)Flow cytometry (1)Mental Disorders (1)Monkey (1)View MoreJournalF1000Research (1)Schizophrenia research (1)

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    NeuN(+) neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure

    Halene, Tobias B.; Kozlenkov, Alexey; Jiang, Yan; Mitchell, Amanda C.; Javidfar, Behnam; Dincer, Aslihan; Park, Royce; Wiseman, Jennifer; Croxson, Paula L.; Giannaris, Eustathia Lela; et al. (2016-02-01)
    Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN(+) nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted.
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    The Resource Identification Initiative: A cultural shift in publishing

    Bandrowski, Anita; Brush, Matthew; Grethe, Jeffery S.; Haendel, Melissa A.; Kennedy, David N.; Hill, Sean; Hof, Patrick R.; Martone, Maryann E.; Pols, Maaike; Tan, Serena; et al. (2015-11-19)
    A central tenet in support of research reproducibility is the ability to uniquely identify research resources, i.e., reagents, tools, and materials that are used to perform experiments. However, current reporting practices for research resources are insufficient to allow humans and algorithms to identify the exact resources that are reported or answer basic questions such as "What other studies used resource X?" To address this issue, the Resource Identification Initiative was launched as a pilot project to improve the reporting standards for research resources in the methods sections of papers and thereby improve identifiability and reproducibility. The pilot engaged over 25 biomedical journal editors from most major publishers, as well as scientists and funding officials. Authors were asked to include Research Resource Identifiers (RRIDs) in their manuscripts prior to publication for three resource types: antibodies, model organisms, and tools (including software and databases). RRIDs represent accession numbers assigned by an authoritative database, e.g., the model organism databases, for each type of resource. To make it easier for authors to obtain RRIDs, resources were aggregated from the appropriate databases and their RRIDs made available in a central web portal ( www.scicrunch.org/resources). RRIDs meet three key criteria: they are machine readable, free to generate and access, and are consistent across publishers and journals. The pilot was launched in February of 2014 and over 300 papers have appeared that report RRIDs. The number of journals participating has expanded from the original 25 to more than 40. Here, we present an overview of the pilot project and its outcomes to date. We show that authors are generally accurate in performing the task of identifying resources and supportive of the goals of the project. We also show that identifiability of the resources pre- and post-pilot showed a dramatic improvement for all three resource types, suggesting that the project has had a significant impact on reproducibility relating to research resources.
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