Prediction of evolutionarily conserved interologs in Mus musculus

<p>Abstract</p> <p>Background</p> <p>Identification of protein-protein interactions is an important first step to understand living systems. High-throughput experimental approaches have accumulated large amount of information on protein-protein interactions in human and other model organisms. Such interaction information has been successfully transferred to other species, in which the experimental data are limited. However, the annotation transfer method could yield false positive interologs due to the lack of conservation of interactions when applied to phylogenetically distant organisms.</p> <p>Results</p> <p>To address this issue, we used phylogenetic profile method to filter false positives in interologs based on the notion that evolutionary conserved interactions show similar patterns of occurrence along the genomes. The approach was applied to <it>Mus musculus</it>, in which the experimentally identified interactions are limited. We first inferred the protein-protein interactions in <it>Mus musculus </it>by using two approaches: i) identifying mouse orthologs of interacting proteins (interologs) based on the experimental protein-protein interaction data from other organisms; and ii) analyzing frequency of mouse ortholog co-occurrence in predicted operons of bacteria. We then filtered possible false-positives in the predicted interactions using the phylogenetic profiles. We found that this filtering method significantly increased the frequency of interacting protein-pairs coexpressed in the same cells/tissues in gene expression omnibus (GEO) database as well as the frequency of interacting protein-pairs shared the similar Gene Ontology (GO) terms for biological processes and cellular localizations. The data supports the notion that phylogenetic profile helps to reduce the number of false positives in interologs.</p> <p>Conclusion</p> <p>We have developed protein-protein interaction database in mouse, which contains 41109 interologs. We have also developed a web interface to facilitate the use of database <url>http://lgsun.grc.nia.nih.gov/mppi/</url>.</p

Rex1/Zfp42 is dispensable for pluripotency in mouse ES cells

Research articl

ELASTOGRAPHY CAN EFFECTIVELY DECREASE THE NUMBER OF FINE-NEEDLE ASPIRATION BIOPSIES IN PATIENTS WITH CALCIFIED THYROID NODULES

When calcification, frequently found in both benign and malignant nodules, is present in thyroid nodules, non-invasive differentiation with ultrasound becomes challenging. The goal of this study was to evaluate the utility of elastography in differentiating calcified thyroid nodules. Consecutive patients (165 patients with 196 nodules) referred for fine-needle aspiration who had undergone both ultrasound elastography and B-mode examinations were analyzed retrospectively. Calcification was present in 45 benign and 20 malignant nodules. On 65 calcified nodules, elastography had 95% sensitivity, 51.1% specificity, 46.3% positive predictive value and 95.8% negative predictive value in detecting malignancy. Twenty-three of 45 benign calcified nodules were correctly diagnosed with elastography compared with 4 of 45 by B-mode ultrasound. Although it is difficult to differentiate benign and malignant calcified thyroid nodules solely with B-mode ultrasound, elastography has the potential to reduce the number of fine-needle aspiration biopsies performed on calcified nodules. (C) 2014 World Federation for Ultrasound in Medicine & Biology.1188Ysciescopu

Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray

The ability to quantitatively measure the expression of all genes in a given tissue or cell with a single assay is an exciting promise of gene-expression profiling technology. An in situ-synthesized 60-mer oligonucleotide microarray designed to detect transcripts from all mouse genes was validated, as well as a set of exogenous RNA controls derived from the yeast genome (made freely available without restriction), which allow quantitative estimation of absolute endogenous transcript abundance

Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data

<p>Abstract</p> <p>Background</p> <p>Target genes of a transcription factor (TF) <it>Pou5f1 </it>(<it>Oct3/4 </it>or <it>Oct4</it>), which is essential for pluripotency maintenance and self-renewal of embryonic stem (ES) cells, have previously been identified based on their response to <it>Pou5f1 </it>manipulation and occurrence of Chromatin-immunoprecipitation (ChIP)-binding sites in promoters. However, many responding genes with binding sites may not be direct targets because response may be mediated by other genes and ChIP-binding site may not be functional in terms of transcription regulation.</p> <p>Results</p> <p>To reduce the number of false positives, we propose to separate responding genes into groups according to direction, magnitude, and time of response, and to apply the false discovery rate (FDR) criterion to each group individually. Using this novel algorithm with stringent statistical criteria (FDR < 0.2) to a compendium of published and new microarray data (3, 6, 12, and 24 hr after <it>Pou5f1 </it>suppression) and published ChIP data, we identified 420 tentative target genes (TTGs) for <it>Pou5f1</it>. The majority of TTGs (372) were down-regulated after <it>Pou5f1 </it>suppression, indicating that the <it>Pou5f1 </it>functions as an activator of gene expression when it binds to promoters. Interestingly, many activated genes are potent suppressors of transcription, which include polycomb genes, zinc finger TFs, chromatin remodeling factors, and suppressors of signaling. Similar analysis showed that <it>Sox2 </it>and <it>Nanog </it>also function mostly as transcription activators in cooperation with <it>Pou5f1</it>.</p> <p>Conclusion</p> <p>We have identified the most reliable sets of direct target genes for key pluripotency genes – <it>Pou5f1</it>, <it>Sox2</it>, and <it>Nanog</it>, and found that they predominantly function as activators of downstream gene expression. Thus, most genes related to cell differentiation are suppressed indirectly.</p

Bidirectional signaling of neuregulin-2 mediates formation of GABAergic synapses and maturation of glutamatergic synapses in newborn granule cells of postnatal hippocampus

Expression of neuregulin-2 (NRG2) is intense in a few regions of the adult brain where neurogenesis persists; however, little is understood about its role in developments of newborn neurons. To study the role of NRG2 in synaptogenesis at different developmental stages, newborn granule cells in rat hippocampal slice cultures were labeled with retrovirus encoding tetracycline-inducible microRNA targeting NRG2 and treated with doxycycline (Dox) at the fourth or seventh postinfection day (dpi). The developmental increase of GABAergic postsynaptic currents (GPSCs) was suppressed by the early Dox treatment (4 dpi), but not by late treatment (7 dpi). The late Dox treatment was used to study the effect of NRG2 depletion specific to excitatory synaptogenesis. The Dox effect on EPSCs emerged 4 d after the impairment in dendritic outgrowth became evident (10 dpi). Notably, Dox treatment abolished the developmental increases of AMPA-receptor mediated EPSCs and the AMPA/NMDA ratio, indicating impaired maturation of glutamatergic synapses. In contrast to GPSCs, Dox effects on EPSCs and dendritic growth were independent of ErbB4 and rescued by concurrent overexpression of NRG2 intracellular domain. These results suggest that forward signaling of NRG2 mediates GABAergic synaptogenesis and its reverse signaling contributes to dendritic outgrowth and maturation of glutamatergic synapses.117Ysciescopu

Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary

<p>Abstract</p> <p>Background</p> <p>The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on <it>ad libitum </it>(AL) feeding with a group on lifespan-extending 40% calorie restriction (CR).</p> <p>Results</p> <p>We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months), whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis.</p> <p>Conclusion</p> <p>Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary.</p

Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity

Comparison of the transcriptomes of pluripotent embryonic stem cells, multipotent adult progenitor cells and lineage restricted mesenchymal stem cells identified a unique gene expression profile of multipotent adult progenitor cells