Perfluorooctanoate suppresses spheroid attachment on endometrial epithelial cells through peroxisome proliferator-activated receptor alpha and down-regulation of Wnt signaling

Exposure of animals to perfluorooctanoic acid (PFOA), a surfactant used in emulsion polymerization processes causes early pregnancy loss, delayed growth and development of fetuses. The mechanisms of action are largely unknown. We studied the effect of PFOA on implantation using an in vitro spheroid-endometrial cell co-culture model. PFOA (10-100μM) significantly reduced Jeg-3 spheroid attachment on RL95-2 endometrial cells. PFOA also suppressed β-catenin expression in Jeg-3 cells. The Wnt agonist Wnt3a stimulated β-catenin expression in Jeg-3 cells and reversed the PFOA suppression of the spheroid attachment. The putative PFOA receptors (PPARα, β, γ) present in both cell lines were not affected by PFOA (0.01-100μM). The PPARα antagonist MK886 restored the β-catenin and E-cadherin expression levels in Jeg-3 cells and reversed the suppression of the spheroid attachment caused by PFOA. Taken together, PFOA suppresses spheroid attachment through PPARα and Wnt signaling pathways via down-regulation of β-catenin and E-cadherin expression.postprin

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses spheroids attachment on endometrial epithelial cells through the down-regulation of the Wnt-signaling pathway

The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects embryo development, implantation and fertility in humans. The underlying molecular mechanism by which TCDD suppresses implantation remains largely unknown. We used the trophoblastic spheroids (embryo surrogate)-endometrial cells co-culture assay to study the attachment of trophoblastic spheroids (BeWo and Jeg-3) onto the endometrial epithelial (RL95-2 and Ishikawa) cells. TCDD dose-dependently induced cytochrome P450 1A1 (Cyp1A1) expression in trophoblastic and endometrial epithelial cells. Moreover, TCDD at 1 and 10. nM suppressed β-catenin (a Wnt-signaling molecule) and E-cadherin expression, as well as spheroids attachment onto endometrial cells. Interestingly, activation of the canonical Wnt-signaling pathway via Wnt3a or lithium chloride reverted the suppressive effect of TCDD on β-catenin and E-cadherin expressions in the BeWo and RL95-2 cells, and restored the spheroids attachment rate to be comparable to the untreated controls. Taken together, TCDD induces Cyp1A1 expression, modulates the Wnt-signaling pathway and suppresses spheroids attachment onto endometrial cells. © 2011 Elsevier Inc.postprin

The endocrine disruptor TCDD modulates microRNA expression in preimplantation mouse embryos and spheroids attachment on human endometrial epithelial cells in vitro

Conference Theme: The Intersection Between Genetics, Genomics, and Reproductive BiologyThe endocrine disruptor (ED) is an exogenous substance that acts on the endocrine system and modulates normal physiological functions of the body. Although EDs such as 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) affect normal reproductive function in humans and affects the growth and reproductive functions in rodents, the underlying mechanism that modulates these changes remains unclear. Accumulating evidence suggested preimplantation embryo development is controlled by ...postprintThe 43rd Annual Meeting of the Society for the Study of Reproduction (SSR), Milwaukee, WI., 30 July-3 August 2010. In Biology of Reproduction, 2010, v. 83 Meeting abstracts, p. 62, abstract no. 27

Haemodynamic consequences of targeted single- and dual-site right ventricular pacing in adults with congenital heart disease undergoing surgical pulmonary valve replacement

Aims The purpose of this study was to create an epicardial electroanatomic map of the right ventricle (RV) and then apply post-operative-targeted single- and dual-site RV temporary pacing with measurement of haemodynamic parameters. Cardiac resynchronization therapy is an established treatment for symptomatic left ventricular (LV) dysfunction. In congenital heart disease, RV dysfunction is a common cause of morbidity—little is known regarding the potential benefits of CRT in this setting. Methods and results Sixteen adults (age = 32 ± 8 years; 6 M, 10 F) with right bundle branch block (RBBB) and repaired tetralogy of Fallot (n = 8) or corrected congenital pulmonary stenosis (n = 8) undergoing surgical pulmonary valve replacement (PVR) for pulmonary regurgitation underwent epicardial RV mapping and haemodynamic assessment of random pacing configurations including the site of latest RV activation. The pre-operative pulmonary regurgitant fraction was 49 ± 10%; mean LV end-diastolic volume (EDV) 85 ± 19 mL/min/m2 and RVEDV 183 ± 89 mL/min/m2 on cardiac magnetic resonance imaging. The mean pre-operative QRS duration is 136 ± 26 ms. The commonest site of latest activation was the RV free wall and DDD pacing here alone or combined with RV apical pacing resulted in significant increases in cardiac output (CO) vs. AAI pacing (P < 0.01 all measures). DDDRV alternative site pacing significantly improved CO by 16% vs. AAI (P = 0.018), and 8.5% vs. DDDRV apical pacing (P = 0.02). Conclusion Single-site RV pacing targeted to the region of latest activation in patients with RBBB undergoing PVR induces acute improvements in haemodynamics and supports the concept of ‘RV CRT’. Targeted pacing in such patients has therapeutic potential both post-operatively and in the long term

An unusual S-adenosylmethionine synthetase gene from dinoflagellate is methylated

Background: S-Adenosylmethionine synthetase (AdoMetS) catalyzes the formation of S-Adenosylmethionine (AdoMet), the major methyl group donor in cells. AdoMet-mediated methylation of DNA is known to have regulatory effects on DNA transcription and chromosome structure. Transcription of environmental-responsive genes was demonstrated to be mediated via DNA methylation in dinoflagellates. Results: A full-length cDNA encoding AdoMetS was cloned from the dinoflagellate Crypthecodinium cohnii. Phylogenetic analysis suggests that the CcAdoMetS gene, is associated with the clade of higher plant orthrologues, and not to the clade of the animal orthrologues. Surprisingly, three extra stretches of residues ( 8 to 19 amino acids) were found on CcAdoMetS, when compared to other members of this usually conserved protein family. Modeled on the bacterial AdeMetS, two of the extra loops are located close to the methionine binding site. Despite this, the CcAdoMetS was able to rescue the corresponding mutant of budding yeast. Southern analysis, coupled with methylation-sensitive and insensitive enzyme digestion of C. cohnii genomic DNA, demonstrated that the AdoMetS gene is itself methylated. The increase in digestibility of methylation-sensitive enzymes on AdoMet synthetase gene observed following the addition of DNA methylation inhibitors L-ethionine and 5-azacytidine suggests the presence of cytosine methylation sites within CcAdoMetS gene. During the cell cycle, both the transcript and protein levels of CcAdoMetS peaked at the G1 phase. L- ethionine was able to delay the cell cycle at the entry of S phase. A cell cycle delay at the exit of G2/M phase was induced by 5-azacytidine. Conclusion: The present study demonstrates a major role of AdoMet-mediated DNA methylation in the regulation of cell proliferation and that the CcAdoMetS gene is itself methylated

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

The association between internet addiction and psychiatric co-morbidity: A meta-analysis

Background: This study evaluates the association between Internal Addiction (IA) and psychiatric co-morbidity in the literature.Methods: Meta-analyses were conducted on cross-sectional, case-control and cohort studies which examined the relationship between IA and psychiatric co-morbidity. Selected studies were extracted from major online databases. The inclusion criteria are as follows: 1) studies conducted on human subjects; 2) IA and psychiatric co-morbidity were assessed by standardised questionnaires; and 3) availability of adequate information to calculate the effect size. Random-effects models were used to calculate the aggregate prevalence and the pooled odds ratios (OR).Results: Eight studies comprising 1641 patients suffering from IA and 11210 controls were included. Our analyses demonstrated a significant and positive association between IA and alcohol abuse (OR = 3.05, 95% CI = 2.14-4.37, z = 6.12, P < 0.001), attention deficit and hyperactivity (OR = 2.85, 95% CI = 2.15-3.77, z = 7.27, P < 0.001), depression (OR = 2.77, 95% CI = 2.04-3.75, z = 6.55, P < 0.001) and anxiety (OR = 2.70, 95% CI = 1.46-4.97, z = 3.18, P = 0.001).Conclusions: IA is significantly associated with alcohol abuse, attention deficit and hyperactivity, depression and anxiety. © 2014 Ho et al.; licensee BioMed Central Ltd

Search for supersymmetry in events with four or more leptons in √s =13 TeV pp collisions with ATLAS

Results from a search for supersymmetry in events with four or more charged leptons (electrons, muons and taus) are presented. The analysis uses a data sample corresponding to 36.1 fb −1 of proton-proton collisions delivered by the Large Hadron Collider at s √ =13 TeV and recorded by the ATLAS detector. Four-lepton signal regions with up to two hadronically decaying taus are designed to target a range of supersymmetric scenarios that can be either enriched in or depleted of events involving the production and decay of a Z boson. Data yields are consistent with Standard Model expectations and results are used to set upper limits on the event yields from processes beyond the Standard Model. Exclusion limits are set at the 95% confidence level in simplified models of General Gauge Mediated supersymmetry, where higgsino masses are excluded up to 295 GeV. In R -parity-violating simplified models with decays of the lightest supersymmetric particle to charged leptons, lower limits of 1.46 TeV, 1.06 TeV, and 2.25 TeV are placed on wino, slepton and gluino masses, respectively