Regulation of pituitary MT1 melatonin receptor expression by gonadotrophin-releasing hormone (GnRH) and early growth response factor-1 (Egr-1) : in vivo and in vitro studies

Copyright: © 2014 Bae et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/F020309/1; http://www.bbsrc.ac.uk/home/home.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Web platform vs in-person genetic counselor for return of carrier results from exome sequencing a randomized clinical trial

© 2018 American Medical Association. All rights reserved. IMPORTANCE A critical bottleneck in clinical genomics is the mismatch between large volumes of results and the availability of knowledgeable professionals to return them. OBJECTIVE To test whether a web-based platform is noninferior to a genetic counselor for educating patients about their carrier results from exome sequencing. DESIGN, SETTING, AND PARTICIPANTS A randomized noninferiority trial conducted in a longitudinal sequencing cohort at the National Institutes of Health from February 5, 2014, to December 16, 2016, was used to compare the web-based platform with a genetic counselor. Among the 571 eligible participants, 1 to 7 heterozygous variants were identified in genes that cause a phenotype that is recessively inherited. Surveys were administered after cohort enrollment, immediately following trial education, and 1 month and 6 months later to primarily healthy postreproductive participants who expressed interest in learning their carrier results. Both intention-to-treat and per-protocol analyses were applied. INTERVENTIONS A web-based platform that integrated education on carrier results with personal test results was designed to directly parallel disclosure education by a genetic counselor. The sessions took a mean (SD) time of 21 (10.6), and 27 (9.3) minutes, respectively. MAIN OUTCOMES AND MEASURES The primary outcomes and noninferiority margins (dNI) were knowledge (0 to 8, dNI = -1), test-specific distress (0 to 30, dNI = +1), and decisional conflict (15 to 75, dNI = +6). RESULTS After 462 participants (80.9%) provided consent and were randomized, all but 3 participants (n = 459) completed surveys following education and counseling; 398 (86.1%) completed 1-month surveys and 392 (84.8%) completed 6-month surveys. Participants were predominantly well-educated, non-Hispanic white, married parents; mean (SD) age was 63 (63.1) years and 246 (53.6%) were men. The web platform was noninferior to the genetic counselor on outcomes assessed at 1 and 6 months: knowledge (mean group difference, -0.18; lower limit of 97.5% CI, -0.63; dNI = -1), test-specific distress (median group difference, 0; upper limit of 97.5% CI, 0; dNI = +1), and decisional conflict about choosing to learn results (mean group difference, 1.18; upper limit of 97.5% CI, 2.66; dNI = +6). There were no significant differences between the genetic counselors and web-based platform detected between modes of education delivery in disclosure rates to spouses (151 vs 159; relative risk [RR], 1.04; 95% CI, 0.64-1.69; P > .99), children (103 vs 117; RR, 1.07; 95% CI, 0.85-1.36; P = .59), or siblings (91 vs 78; RR, 1.17; 95% CI, 0.94-1.46; P = .18). CONCLUSIONS AND RELEVANCE This trial demonstrates noninferiority of web-based return of carrier results among postreproductive, mostly healthy adults. Replication studies among younger and more diverse populations are needed to establish generalizability. Yet return of results via a web-based platform may be sufficient for subsets of test results, reserving genetic counselors for return of results with a greater health threat

Detecting rare functional variants using a wavelet-based test on quantitative and qualitative traits

We conducted a genome-wide association study on the Genetic Analysis Workshop 17 simulated unrelated individuals data using a multilocus score test based on wavelet transformation that we proposed recently. Wavelet transformation is an advanced smoothing technique, whereas the currently popular collapsing methods are the simplest way to smooth multilocus genotypes. The wavelet-based test suppresses noise from the data more effectively, which results in lower type I error rates. We chose a level-dependent threshold for the wavelet-based test to suppress the optimal amount of noise according to the data. We propose several remedies to reduce the inflated type I error rate: using a window of fixed size rather than a gene; using the Bonferroni correction rather than comparing to the maxima of test values for multiple testing corrections; and removing the influence of other factors by using residuals for the association test. A wavelet-based test can detect multiple rare functional variants. Type I error rates can be controlled using the wavelet-based test combined with the mentioned remedies

The MIF antagonist ISO-1 attenuates corticosteroid-insensitive inflammation and airways hyperresponsiveness in an ozone-induced model of COPD

Copyright © 2016 Russell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however. Methods. Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from nonsmokers, smokers and COPD patients. To mimic oxidative stress-induced COPD, mice were exposed to ozone for six-weeks and treated with ISO-1, a MIF inhibitor, and/or dexamethasone before each exposure. BAL fluid and lung tissue were collected after the final exposure. Airway hyperresponsiveness (AHR) and lung function were measured using whole body plethysmography. HIF-1α binding to the Mif promoter was determined by Chromatin Immunoprecipitation assays. Results. MIF levels in sputum and BAL macrophages from COPD patients were higher than those from non-smokers, with healthy smokers having intermediate levels. MIF expression correlated with that of HIF-1α in all patients groups and in ozone-exposed mice. BAL cell counts, cytokine mRNA and protein expression in lungs and BAL, including MIF, were elevated in ozone-exposed mice and had increased AHR. Dexamethasone had no effect on these parameters in the mouse but ISO-1 attenuated cell recruitment, cytokine release and AHR. Conclusion MIF and HIF-1α levels are elevated in COPD BAL macrophages and inhibition of MIF function blocks corticosteroid-insensitive lung inflammation and AHR. Inhibition of MIF may provide a novel anti-inflammatory approach in COPD

Impaired perception of facial motion in autism spectrum disorder

Copyright: © 2014 O’Brien et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Facial motion is a special type of biological motion that transmits cues for socio-emotional communication and enables the discrimination of properties such as gender and identity. We used animated average faces to examine the ability of adults with autism spectrum disorders (ASD) to perceive facial motion. Participants completed increasingly difficult tasks involving the discrimination of (1) sequences of facial motion, (2) the identity of individuals based on their facial motion and (3) the gender of individuals. Stimuli were presented in both upright and upside-down orientations to test for the difference in inversion effects often found when comparing ASD with controls in face perception. The ASD group’s performance was impaired relative to the control group in all three tasks and unlike the control group, the individuals with ASD failed to show an inversion effect. These results point to a deficit in facial biological motion processing in people with autism, which we suggest is linked to deficits in lower level motion processing we have previously reported

The impact of lens galaxy environments on the image separation distribution

We study the impact of lens galaxy environments on the image separation distribution of lensed quasars. We account for both environmental convergence and shear, using a joint distribution derived from galaxy formation models calibrated by galaxy-galaxy lensing data and number counts of massive elliptical galaxies. We find that the external field enhances lensing probabilities, particularly at large image separations; the increase is ~30% at \theta=3'' and ~200% at \theta=5'', when we adopt a power-law source luminosity function \Phi(L) \propto L^-2.1. The enhancement is mainly driven by convergence, which boosts both the image separation and magnification bias (for a fixed lens galaxy mass). These effects have been neglected in previous studies of lens statistics. Turning the problem around, we derive the posterior convergence and shear distributions and point out that they are strong functions of image separation; lens systems with larger image separations are more likely to lie in dense environments.Comment: 8 pages, 10 figures, accepted for publication in MNRA

Testing the dark energy with gravitational lensing statistics

We study the redshift distribution of two samples of early-type gravitational lenses, extracted from a larger collection of 122 systems, to constrain the cosmological constant in the LCDM model and the parameters of a set of alternative dark energy models (XCDM, Dvali-Gabadadze-Porrati and Ricci dark energy models), under a spatially flat universe. The likelihood is maximized for $\Omega_\Lambda= 0.70 \pm 0.09$ when considering the sample excluding the SLACS systems (known to be biased towards large image-separation lenses) and no-evolution, and $\Omega_\Lambda= 0.81\pm 0.05$ when limiting to gravitational lenses with image separation larger than 2" and no-evolution. In both cases, results accounting for galaxy evolution are consistent within 1$\sigma$. The present test supports the accelerated expansion, by excluding the null-hypothesis (i.e., $\Omega_\Lambda = 0$) at more than 4$\sigma$, regardless of the chosen sample and assumptions on the galaxy evolution. A comparison between competitive world models is performed by means of the Bayesian information criterion. This shows that the simplest cosmological constant model - that has only one free parameter - is still preferred by the available data on the redshift distribution of gravitational lenses. We perform an analysis of the possible systematic effects, finding that the systematic errors due to sample incompleteness, galaxy evolution and model uncertainties approximately equal the statistical errors, with present-day data. We find that the largest sources of systemic errors are the dynamical normalization and the high-velocity cut-off factor, followed by the faint-end slope of the velocity dispersion function.Comment: 14 pages, 10 figures, accepted for publication in The Astrophysical Journal. Updated to match print versio

Molecular characterisation of protist parasites in human-habituated mountain gorillas (Gorilla beringei beringei), humans and livestock, from Bwindi impenetrable National Park, Uganda

Over 60 % of human emerging infectious diseases are zoonotic, and there is growing evidence of the zooanthroponotic transmission of diseases from humans to livestock and wildlife species, with major implications for public health, economics, and conservation. Zooanthroponoses are of relevance to critically endangered species; amongst these is the mountain gorilla (Gorilla beringei beringei) of Uganda. Here, we assess the occurrence of Cryptosporidium, Cyclospora, Giardia, and Entamoeba infecting mountain gorillas in the Bwindi Impenetrable National Park (BINP), Uganda, using molecular methods. We also assess the occurrence of these parasites in humans and livestock species living in overlapping/adjacent geographical regions

Giant phonon anomalies and central peak due to charge density wave formation in YBa2_2Cu3_3O6.6_{6.6}

The electron-phonon interaction is a major factor influencing the competition between collective instabilities in correlated-electron materials, but its role in driving high-temperature superconductivity in the cuprates remains poorly understood. We have used high-resolution inelastic x-ray scattering to monitor low-energy phonons in YBa$_2$Cu$_3$O$_{6.6}$ (superconducting $\bf T_c = 61$ K), which is close to a charge density wave (CDW) instability. Phonons in a narrow range of momentum space around the CDW ordering vector exhibit extremely large superconductivity-induced lineshape renormalizations. These results imply that the electron-phonon interaction has sufficient strength to generate various anomalies in electronic spectra, but does not contribute significantly to Cooper pairing. In addition, a quasi-elastic "central peak" due to CDW nanodomains is observed in a wide temperature range above and below $\bf T_c$, suggesting that the gradual onset of a spatially inhomogeneous CDW domain state with decreasing temperature is a generic feature of the underdoped cuprates

A lionfish (Pterois miles) invasion has begun in the Mediterranean Sea

Until now, few sightings of the alien lionfish Pterois miles have been reported in the Mediterranean and it was questionable whether the species could invade this region like it has in the western Atlantic. Here, we present evidence from divers and fishermen that lionfish have recently increased in abundance and within a year colonised almost the entire south eastern coast of Cyprus, likely due to sea surface warming. At least 23 different fish are reported of which 6 were removed. Groups of lionfish exhibiting mating behaviour have been noted for the first time in the Mediterranean. Managers need this information and should alert stakeholders to the potential ecological and socio-economic impacts that may arise from a lionfish invasion. Actions could involve incentives to engage divers and fishermen in lionfish removal programmes, as these have worked well at shallow depths in the Caribbean. Given that the Suez Canal has recently been widened and deepened, measures will need to be put in place to help prevent further invasion