No abstract

Background-We recently described "Author-ity," a model for estimating the probability that two articles in MEDLINE, sharing the same author name, were written by the same individual. Features include shared title words, journal name, coauthors, medical subject headings, language, affiliations, and author name features (middle initial, suffix, and prevalence in MEDLINE). Here we test the hypothesis that the Author-ity model will suffice to disambiguate author names for the vast majority of articles in MEDLINE.Methods-Enhancements include: (a) incorporating first names and their variants, email addresses, and correlations between specific last names and affiliation words; (b) new methods of generating large unbiased training sets; (c) new methods for estimating the prior probability; (d) a weighted least squares algorithm for correcting transitivity violations; and (e) a maximum likelihood based agglomerative algorithm for computing clusters of articles that represent inferred author-individuals.Results-Pairwise comparisons were computed for all author names on all 15.3 million articles in MEDLINE (2006 baseline), that share last name and first initial, to create Author-ity 2006, a database that has each name on each article assigned to one of 6.7 million inferred author-individual clusters. Recall is estimated at ~98.8%. Lumping (putting two different individuals into the same cluster) affects ~0.5% of clusters, whereas splitting (assigning articles written by the same individual to >1 cluster) affects ~2% of articles.Impact-The Author-ity model can be applied generally to other bibliographic databases. Author name disambiguation allows information retrieval and data integration to become person-centered, not just document-centered, setting the stage for new data mining and social network tools that will facilitate the analysis of scholarly publishing and collaboration behavior.Availability-The Author-ity 2006 database is available for nonprofit academic research, and can be freely queried via http://arrowsmith.psych.uic.edu.

We have characterized the expression of microRNAs and selected microRNA precursors within several synaptic fractions of adult mouse forebrain, including synaptoneurosomes, synaptosomes and isolated postsynaptic densities, using methods of microRNA microarray, real time qRT-PCR, Northern blotting and immunopurification using anti-PSD95 antibody. The majority of brain microRNAs (especially microRNAs known to be expressed in pyramidal neurons) are detectably expressed in synaptic fractions, and a subset of microRNAs is significantly enriched in synaptic fractions relative to total forebrain homogenate. MicroRNA precursors are also detectable in synaptic fractions at levels that are comparable to whole tissue. Whereas mature microRNAs are predominantly associated with soluble components of the synaptic fractions, microRNA precursors are predominantly associated with postsynaptic densities. For seven microRNAs examined, there was a significant correlation between the relative synaptic enrichment of the precursor and the relative synaptic enrichment of the corresponding mature microRNA. These findings support the proposal that microRNAs are formed, at least in part, via processing of microRNA precursors locally within dendritic spines. Dicer is expressed in postsynaptic densities but is enzymatically inactive until conditions that activate calpain cause its liberation; thus, we propose that synaptic stimulation may lead to local processing of microRNA precursors in proximity to the synapse.

BackgroundRecent studies suggest that alterations in expression of genes, including those which regulate neural and structural plasticity, may be crucial in the pathogenesis of depression. MicroRNAs (miRNAs) are newly discovered regulators of gene expression that have recently been implicated in a variety of human diseases, including neuropsychiatric diseases.Methodology/Principal FindingsThe present study was undertaken to examine whether the miRNA network is altered in the brain of depressed suicide subjects. Expression of miRNAs was measured in prefrontal cortex (Brodmann Area 9) of antidepressant-free depressed suicide (n = 18) and well-matched non-psychiatric control subjects (n = 17) using multiplex RT-PCR plates. We found that overall miRNA expression was significantly and globally down-regulated in prefrontal cortex of depressed suicide subjects. Using individual tests of statistical significance, 21 miRNAs were significantly decreased at p = 0.05 or better. Many of the down-regulated miRNAs were encoded at nearby chromosomal loci, shared motifs within the 5′-seeds, and shared putative mRNA targets, several of which have been implicated in depression. In addition, a set of 29 miRNAs, whose expression was not pairwise correlated in the normal controls, showed a high degree of co-regulation across individuals in the depressed suicide group.Conclusions/SignificanceThe findings show widespread changes in miRNA expression that are likely to participate in pathogenesis of major depression and/or suicide. Further studies are needed to identify whether the miRNA changes lead to altered expression of prefrontal cortex mRNAs, either directly (by acting as miRNA targets) or indirectly (e.g., by affecting transcription factors).

No abstract