Fragmentation of the large subunit ribosomal RNA gene in oyster mitochondrial genomes

<p>Abstract</p> <p>Background</p> <p>Discontinuous genes have been observed in bacteria, archaea, and eukaryotic nuclei, mitochondria and chloroplasts. Gene discontinuity occurs in multiple forms: the two most frequent forms result from introns that are spliced out of the RNA and the resulting exons are spliced together to form a single transcript, and fragmented gene transcripts that are not covalently attached post-transcriptionally. Within the past few years, fragmented ribosomal RNA (rRNA) genes have been discovered in bilateral metazoan mitochondria, all within a group of related oysters.</p> <p>Results</p> <p>In this study, we have characterized this fragmentation with comparative analysis and experimentation. We present secondary structures, modeled using comparative sequence analysis of the discontinuous mitochondrial large subunit rRNA genes of the cupped oysters <it>C. virginica, C. gigas</it>, and <it>C. hongkongensis</it>. Comparative structure models for the large subunit rRNA in each of the three oyster species are generally similar to those for other bilateral metazoans. We also used RT-PCR and analyzed ESTs to determine if the two fragmented LSU rRNAs are spliced together. The two segments are transcribed separately, and not spliced together although they still form functional rRNAs and ribosomes.</p> <p>Conclusions</p> <p>Although many examples of discontinuous ribosomal genes have been documented in bacteria and archaea, as well as the nuclei, chloroplasts, and mitochondria of eukaryotes, oysters are some of the first characterized examples of fragmented bilateral animal mitochondrial rRNA genes. The secondary structures of the oyster LSU rRNA fragments have been predicted on the basis of previous comparative metazoan mitochondrial LSU rRNA structure models.</p

Periostin promotes invasion and anchorage-independent growth in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of human cancer. Typically HNSCC cells show persistent invasion that frequently leads to local recurrence and distant lymphatic metastasis. However, molecular mechanisms associated with invasion and metastasis of HNSCC remain poorly understood. Here we identified Periostin as an invasion promoting factor in HNSCC by comparing the gene expression profiles between parent HNSCC cells and a highly invasive clone. Indeed, Periostin overexpression promoted the invasion and anchorage independent growth both in vitro and in vivo in HNSCC cells. Moreover, Periostin overexpressing cells spontaneously metastasized to cervical lymph nodes and to the lung through their aggressive invasiveness in an orthotopic mouse model of HNSCC. Interestingly, Periostin was highly expressed in HNSCCs in comparison with normal tissues, and the level of Periostin expression was well correlated with the invasiveness of HNSCC cases. In summary, these findings suggest that Periostin plays an important role for invasion and anchorage independent growth in the metastatic process of HNSCC

Mitochondrial cytochrome oxidase I gene sequences support an Asian origin for the Portuguese oyster Crassostrea angulata

The Portuguese oyster Crassostrea angulata (Lamarck, 1819) was long assumed to be native to the northeastern Atlantic, however, a number of lines of evidence now indicate that it is a close relative, or identical, to the Asian Pacific oyster C. gigas (Thunberg, 1793). Three hypotheses have been proposed to explain how this strikingly disjunct geographic distribution may have come about: ancient vicariance events, recent anthropogenic introduction to Asia and recent anthropogenic introduction to Europe. We have performed a molecular phylogenetic analysis of C. angulata based on mitochondrial DNA sequence data for a 579-nucleotide fragment of cytochrome oxidase I. Our results show that Portuguese oyster haplotypes cluster robustly within a clade of Asian congeners and are closely related, but not identical, to C. gigas from Japan. The mitochondrial data are the first to show that Portuguese oysters are genetically distinct from geographically representative samples of Japanese Pacific oysters. Our phylogenetic analyses are consistent with a recent introduction of C. angulata to Europe either from a non-Japanese Asian source population or from a subsequently displaced Japanese source population. Genetic characterization of Pacific oysters throughout their Asian range is necessary to fully reveal the phylogenetic relationships among Portuguese and Pacific oysters.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42028/1/227-131-3-497_81310497.pd

X-ray emitting young stars in the Orion Nebula

The Orion Nebula Cluster and the molecular cloud in its vicinity have been observed with the ACIS-I detector on board the Chandra X-ray Observatory with 23 hours exposure. We detect 1075 X-ray sources: 91% are spatially associated with known stellar members of the cluster, and 7% are newly identified deeply embedded cloud members. This provides the largest X-ray study of a pre-main sequence stellar population. We examine here the X-ray properties of Orion young stars as a function of mass. Results include: (a) the discovery of rapid variability in the O9.5 31 M_o star \theta^2A Ori, and several early B stars, inconsistent with the standard model of X-ray production in small wind shocks; (b) support for the hypothesis that intermediate-mass mid-B through A type stars do not themselves produce significant X-ray emission; (c) confirmation that low-mass G- through M-type T Tauri stars exhibit powerful flaring but typically at luminosities considerably below the `saturation' level; (d) confirmation that the presence or absence of a circumstellar disk has no discernable effect on X-ray emission; (e) evidence that T Tauri plasma temperatures are often very high with T >= 100 MK, even when luminosities are modest and flaring is not evident; and (f) detection of the largest sample of pre-main sequence very low mass objects showing high flaring levels and a decline in magnetic activity as they evolve into L- and T-type brown dwarfs.Comment: 82 pages, 16 figures, 6 tables. To appear in the Astrophysical Journal. For a version with high quality images and electronic tables, see ftp://ftp.astro.psu.edu/pub/edf/orion1

Effects of IRF5 Lupus Risk Haplotype on Pathways Predicted to Influence B Cell Functions

Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype. Pathway analysis using expressed genes from the significant gene sets impacted by the IRF5 risk haplotype confirmed significant correlation with the interferon pathway, Toll-like receptor pathway, and the B-cell receptor pathway. SLE patients with the IRF5 risk haplotype have a heightened interferon signature, even in an unstimulated state (P = 0.011), while patients with the IRF5 protective haplotype have a B cell interferon signature similar to that of controls. These results identify multiple genes in functionally significant pathways which are affected by IRF5 genotype. They also establish the IRF5 risk haplotype as a key determinant of not only the interferon response, but also other B-cell pathways involved in SLE

RBPJ Mutations Identified in Two Families Affected by Adams-Oliver Syndrome

Through exome resequencing, we identified two unique mutations in recombination signal binding protein for immunoglobulin kappa J (RBPJ) in two independent families affected by Adams-Oliver syndrome (AOS), a rare multiple-malformation disorder consisting primarily of aplasia cutis congenita of the vertex scalp and transverse terminal limb defects. These identified mutations link RBPJ, the primary transcriptional regulator for the Notch pathway, with AOS, a human genetic disorder. Functional assays confirmed impaired DNA binding of mutated RBPJ, placing it among other notch-pathway proteins altered in human genetic syndromes

Identification and replication of RNA-Seq gene network modules associated with depression severity

Genomic variation underlying major depressive disorder (MDD) likely involves the interaction and regulation of multiple genes in a network. Data-driven co-expression network module inference has the potential to account for variation within regulatory networks, reduce the dimensionality of RNA-Seq data, and detect significant geneexpression modules associated with depression severity. We performed an RNA-Seq gene co-expression network analysis of mRNA data obtained from the peripheral blood mononuclear cells of unmedicated MDD (n = 78) and healthy control (n = 79) subjects. Across the combined MDD and HC groups, we assigned genes into modules using hierarchical clustering with a dynamic tree cut method and projected the expression data onto a lower-dimensional module space by computing the single-sample gene set enrichment score of each module. We tested the singlesample scores of each module for association with levels of depression severity measured by the Montgomery-Åsberg Depression Scale (MADRS). Independent of MDD status, we identified 23 gene modules from the co-expression network. Two modules were significantly associated with the MADRS score after multiple comparison adjustment (adjusted p = 0.009, 0.028 at 0.05 FDR threshold), and one of these modules replicated in a previous RNA-Seq study of MDD (p = 0.03). The two MADRS-associated modules contain genes previously implicated in mood disorders and show enrichment of apoptosis and B cell receptor signaling. The genes in these modules show a correlation between network centrality and univariate association with depression, suggesting that intramodular hub genes are more likely to be related to MDD compared to other genes in a module