Altered Gene Expression Encoding Cytochines, Grow Factors and Cell Cycle Regulators in the Endometrium of Women with Chronic Endometritis

To evaluate the expression of genes encoding cytokines, grow factors and cell cycle regulators in the proliferative endometrium of women with chronic endometritis (CE) compared to controls. We performed a case-control study on seven women with CE as diagnosed by hysteroscopy and histology (Cases) compared to six women without CE (Controls). All women underwent diagnostic hysteroscopy plus endometrial biopsy during the mid-proliferative phase of the menstrual cycle. Endometrial samples were divided into two different aliquots for histological and molecular analyses. The endometrial expression profile of 16 genes encoding proteins involved in the inflammatory process, proliferation and cell cycle regulation/apoptosis was assessed by using high-throughput qPCR. Study endpoints were between-group differences in the expression of VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1, BAX and IL12. RESULTS: VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1 were significantly overexpressed in women with CE compared to controls, while BAX and IL12 had similar expression between groups. In women with CE, we found an altered endometrial expression of genes involved in inflammatory, cell proliferation, and apoptosis processes. The dominance of proliferative and anti-apoptotic activity in CE may potentially promote the development of polyps and hyperplastic lesions

Mosquitoes LTR Retrotransposons: A Deeper View into the Genomic Sequence of Culex quinquefasciatus

A set of 67 novel LTR-retrotransposon has been identified by in silico analyses of the Culex quinquefasciatus genome using the LTR_STRUC program. The phylogenetic analysis shows that 29 novel and putatively functional LTR-retrotransposons detected belong to the Ty3/gypsy group. Our results demonstrate that, by considering only families containing potentially autonomous LTR-retrotransposons, they account for about 1% of the genome of C. quinquefasciatus. In previous studies it has been estimated that 29% of the genome of C. quinquefasciatus is occupied by mobile genetic elements

Features of the non-autonomous LTR retrotransposons identified in this paper.

<p>For each non-autonomous element is reported the supercontig in which a representative element can be found, the overall length, the LTR size, the tRNA complementary to the PBS. It is also indicated the position, the period and the copies of the repeated DNA contained in the elements listed. The entropy value gives an estimation of the complexity of the repeats (see main text). The portion occupied by repeats in terms of % of the total size of the element is also indicated (column %).</p

Evolutionary relationships of <i>C. quinquefasciatus</i> LTR-retrotransposons.

<p>Phylogenetic relationships of the LTR retrotransposons based on the amino acids alignment of the conserved RT, RNase H and INT domains. The clades in which fall retrotransposons detected in this paper are indicated with different colors, along with the most common tRNA complementary to the PBS is indicated for each homogeneous group. Elements from this study are indicated as “cpgypsy_” followed by a number. AAGYPSY# elements are LTR retrotransposons identified in previous analyses <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030770#pone.0030770-Minervini1" target="_blank">[17]</a>. The N-J bootstrap values supporting the internal branches are indicated at the nodes. Only bootstrap values greater than 50% are reported. Bel-like elements were used as outgroup. Note that, for families composed of two or more copies (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030770#pone-0030770-t001" target="_blank">table 1</a>), representative elements (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030770#pone.0030770.s001" target="_blank">file S1</a>) were used for the phylogenetic analyses.</p

The contribution of LTR-retrotransposons to <i>C. quinquefasciatus</i> gene organization.

<p>For each insertions detected in proximity (+/− 5 Kbp) or into genes are reported the kind of interaction (upstream, downstream, exon, intron), the Vectorbase identifier of the gene, its description and its position in the supercontig.</p

Evolutionary relationships of <i>Osvaldo</i>-like elements of <i>C. quinquefasciatus</i> LTR-retrotransposons.

<p>Phylogenetic relationships of the <i>Osvaldo</i>-like retrotransposons based on the amino acids alignment of the conserved RT, RNase H and INT domains CPGYPSY5 and AAGYPSY# are LTR retrotransposons identified in previous analyses <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030770#pone.0030770-Minervini1" target="_blank">[17]</a>. Elements “gypsy ELE ###” were retrieved from the TEfam database. The N-J bootstrap values supporting the internal branches are indicated at the nodes. Only bootstrap values greater than 50% are reported. Bel-like elements were used as outgroup.</p

Contribution of the non-autonomous elements identified in this paper to the formation of mature mRNAs of <i>C. quinquefasciatus</i> genes.

<p>Contribution of the non-autonomous elements identified in this paper to the formation of mature mRNAs of <i>C. quinquefasciatus</i> genes.</p

Structural features of the <i>C. quinquefasciatus</i> LTR-retrotransposons detected.

<p>“Lineage” indicates the major lineage they belong to; the estimated copy number detected by BLAST analysis is indicated in the column “copies”; copies enumerated in column “Elements” are those identified by the LTR_STRUC program; “length” indicates the overall element length; “ORFs” indicates the number of ORFs detected in each element; TSD shows the target sequence duplicated upon insertion, Primer Binding Site (PBS); LTR indicates the LTR length; supercontig indicates the supercontig where a given element was identified. %LNI: percent LTRs nucleotide identity.</p><p>Note that two values are reported in the LTRs column if the two LTRs of an element differ in size. “frag” indicates fragmented coding regions.</p

Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release

G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT), its associated G protein, and β-arrestins are on and within neuronal mitochondria. We discovered that the ligand melatonin is exclusively synthesized in the mitochondrial matrix and released by the organelle activating the mitochondrial MT signal-transduction pathway inhibiting stress-mediated cytochrome release and caspase activation. These findings coupled with our observation that mitochondrial MT overexpression reduces ischemic brain injury in mice delineate a mitochondrial GPCR mechanism contributing to the neuroprotective action of melatonin. We propose a new term, automitocrine, analogous to autocrine when a similar phenomenon occurs at the cellular level, to describe this unexpected intracellular organelle ligand-receptor pathway that opens a new research avenue investigating mitochondrial GPCR biology