Circulating microRNA Profile throughout the Menstrual Cycle

<div><p>Normal physiological variables, such as age and gender, contribute to alterations in circulating microRNA (miRNA) expression levels. The changes in the female body during the menstrual cycle can also be reflected in plasma miRNA expression levels. Therefore, this study aimed to determine the plasma miRNA profile of healthy women during the menstrual cycle and to assess which circulating miRNAs are derived from blood cells. The plasma miRNA expression profiles in nine healthy women were determined by quantitative real time PCR using Exiqon Human Panel I assays from four time-points of the menstrual cycle. This platform was also used for studying miRNAs from pooled whole blood RNA samples at the same four time-points. Our results indicated that circulating miRNA expression levels in healthy women were not significantly altered by the processes occurring during the menstrual cycle. No significant differences in plasma miRNA expression levels were observed between the menstrual cycle time-points, but the number of detected miRNAs showed considerable variation among the studied individuals. miRNA analysis from whole blood samples revealed that majority of miRNAs in plasma are derived from blood cells. The most abundant miRNA in plasma and blood was hsa-miR-451a, but a number of miRNAs were only detected in one or the other sample type. In conclusion, our data suggest that the changes in the female body during the menstrual cycle do not affect the expression of circulating miRNAs at measurable levels.</p> </div

Additional file 3: Figure S1. of Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene

A non-random X-chromosome inactivation pattern of leiomyoma specimen of the BML patient. HpaII + denotes enzyme-digested DNA and HpaII − means undigested DNA. (PPTX 46 kb

Additional file 1: of Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene

Supplementary methods. DNA extraction and sequencing. (DOCX 21 kb

Deep Quantitative Proteomics Reveals Extensive Metabolic Reprogramming and Cancer-Like Changes of Ectopic Endometriotic Stromal Cells

Endometriosis is a prevalent health condition in women of reproductive age characterized by ectopic growth of endometrial-like tissue in the extrauterine environment. Thorough understanding of the molecular mechanisms underlying the disease is still incomplete. We dissected eutopic and ectopic endometrial primary stromal cell proteomes to a depth of nearly 6900 proteins using quantitative mass spectrometry with a spike-in SILAC standard. Acquired data revealed metabolic reprogramming of ectopic stromal cells with extensive upregulation of glycolysis and downregulation of oxidative respiration, a widespread metabolic phenotype known as the Warburg effect and previously described in many cancers. These changes in metabolism are additionally accompanied by attenuated aerobic respiration of ectopic endometrial stromal cells as measured by live-cell oximetry and by altered mRNA levels of respective enzyme complexes. Our results additionally highlight other molecular changes of ectopic endometriotic stromal cells indicating reduced apoptotic potential, increased cellular invasiveness and adhesiveness, and altered immune function. Altogether, these comprehensive proteomics data refine the current understanding of endometriosis pathogenesis and present new avenues for therapies

High-Throughput Sequencing Approach Uncovers the miRNome of Peritoneal Endometriotic Lesions and Adjacent Healthy Tissues

<div><p>Accumulating data have shown the involvement of microRNAs (miRNAs) in endometriosis pathogenesis. In this study, we used a novel approach to determine the endometriotic lesion-specific miRNAs by high-throughput small RNA sequencing of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissues together with eutopic endometria of the same patients. We found five miRNAs specific to epithelial cells – miR-34c, miR-449a, miR-200a, miR-200b and miR-141 showing significantly higher expression in peritoneal endometriotic lesions compared to healthy peritoneal tissues. We also determined the expression levels of miR-200 family target genes E-cadherin, ZEB1 and ZEB2 and found that the expression level of E-cadherin was significantly higher in endometriotic lesions compared to healthy tissues. Further evaluation verified that studied miRNAs could be used as diagnostic markers for confirming the presence of endometrial cells in endometriotic lesion biopsy samples. Furthermore, we demonstrated that the miRNA profile of peritoneal endometriotic lesion biopsies is largely masked by the surrounding peritoneal tissue, challenging the discovery of an accurate lesion-specific miRNA profile. Taken together, our findings indicate that only particular miRNAs with a significantly higher expression in endometriotic cells can be detected from lesion biopsies, and can serve as diagnostic markers for endometriosis.</p></div

Receiver operating characteristic (ROC) curve analysis for combined signature of miR449a/200a/200b.

<p>The miRNA expression signature of miR-449a/200a/200b discriminated endometriotic lesions (n = 22) from non-diseased tissues (n = 24) with 95.8% sensitivity and 95.4% specificity. Area under the ROC curve (AUC) is 0.95 (95% CI, 0.83–0.99).</p

The expression of selected miRNAs in endometriotic lesions (n = 22), histologically unconfirmed lesions (n = 10) and healthy tissues (n = 14) using qRT-PCR.

<p>The fold changes for endometriotic lesions and unconfirmed lesions are calculated relative to healthy tissues using the 2^−ΔΔCT method <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112630#pone.0112630-Livak1" target="_blank">[26]</a>. The error bars denote SEM (standard error of the mean). * Denotes comparison of endometriotic lesions with healthy tissues, <i>P</i><0.0001.</p

Peer Effects and Voluntary Green Building Certification

Empirical evidence is provided to show that peer effects have statistically significant and positive impacts on the diffusion of green building certificates. Application and approval records of green certificates by commercial buildings in NY and AZ are used. The challenge of self-selection is addressed by the usage of fixed effects and the challenge of reflection is addressed by the time lag delay between a building’s application and its approval. Empirical results show that an additional approved LEED certificate within a zip code will increase the probability of a commercial building in the same zip code to apply for a LEED certificate by 3–4 percentage points; an additional approved Energy Star certificate within a zip code will increase the probability of a commercial building in the same zip code to apply for an Energy Star certificate by 1–2 percentage points

Additional file 7: of The influence of menstrual cycle and endometriosis on endometrial methylome

Menstrual cycle phase specific genes. The list of late-secretory and menstrual phase specific hyper- and hypomethylated genes. (XLSX 28 kb

風俗 金魚傳 第二編

An Edo-period illustrated novel of the gesaku genre.Dimensions: 7 x 4⅝ x ⅛ in. (17.78 x 11.75 x 0.32 cm)Gift of Barry Rosenstee