The human myometrium differentially expresses mTOR signalling components before and during pregnancy: Evidence for regulation by progesterone

Emerging studies implicate the signalling of the mammalian target of rapamycin (mTOR) in a number of reproductive functions. To this date, there are no data regarding the expression of mTOR signalling components in the human myometrium during pregnancy. We hypothesized that mTOR-related genes might be differentially expressed in term or preterm labour as well as in labour or non-labour myometria during pregnancy. Using quantitative RT-PCR we demonstrate for first time that there is a significant downregulation of mTOR, DEPTOR, and Raptor in preterm labouring myometria when compared to non-pregnant tissues taken from the same area (lower segment). We used an immortalized myometrial cell line (ULTR) as an in vitro model to dissect further mTOR signalling. In ULTR cells DEPTOR and Rictor had a cytoplasmic distribution, whereas mTOR and Raptor were detected in the cytoplasm and the nucleus, indicative of mTORC1 shuttling. Treatment with inflammatory cytokines caused only minor changes in gene expression of these components, whereas progesterone caused significant down-regulation. We performed a non-biased gene expression analysis of ULTR cells using Nimblegen human gene expression microarray (n = 3), and selected genes were validated by quantitative RT-PCR in progesterone treated myometrial cells. Progesterone significantly down-regulated key components of the mTOR pathway. We conclude that the human myometrium differentially expresses mTOR signalling components and they can be regulated by progesterone. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.This research was funded by National Institutes of Health Grant ESO12961

Inhibitory Effect of TIMP Influences the Morphology of Varicose Veins

AbstractObjectivesImbalance of matrix metalloproteinase enzymes (MMP) and their inhibitors (TIMPs) may contribute to the development of varicose veins. We hypothesised that, histological changes in varicose vein wall correlate with alterations in expression of MMP/TIMP.MethodsVaricose veins (n = 26) were compared with great saphenous vein (GSV) segments (n = 11) from arterial bypass, and with arm and neck veins from fistula and carotid operations (n = 13). Varicose vein wall thickness was measured, enabling categorisation as atrophic and hypertrophic. MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively analysed by immunohistochemistry.ResultsThere was significantly higher expression of TIMP-2 (immunopositive area 4.34% versus 0.26%), linked with connective tissue accumulation in the tunica media of varicose veins as compared with arm and neck vein controls. TIMP-2 and TIMP-3 expression was higher in hypertrophic than atrophic segments (3.2% versus 0.99% for TIMP-2, 1.7% versus 0.08% for TIMP-3). Similarly, TIMP-2 and TIMP-3 had elevated expression in the thicker proximal varicose vein segments compared to distal (4.3% versus 1.3% for TIMP-2 and 0.94% versus 0.41% for TIMP-3).ConclusionsThis study linked morphological changes in varicose vein walls with MMP/TIMP balance. A higher TIMP expression favours deposition of connective tissue and thus thicker vein wall, reducing matrix turnover by suppression of protease activity

The highest frequency detection of a radio relic : 16 GHz AMI observations of the 'Sausage' cluster

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society: Letters. © 2014 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.We observed the cluster CIZA J2242.8+5301 with the Arcminute Microkelvin Imager at 16 GHz and present the first high radio-frequency detection of diffuse, non-thermal cluster emission. This cluster hosts a variety of bright, extended, steep-spectrum synchrotron-emitting radio sources, associated with the intracluster medium, called radio relics. Most notably, the northern, Mpc-wide, narrow relic provides strong evidence for diffusive shock acceleration in clusters. We detect a puzzling, flat-spectrum, diffuse extension of the southern relic, which is not visible in the lower radio-frequency maps. The northern radio relic is unequivocally detected and measures an integrated flux of 1.2 ± 0.3 mJy. While the low-frequency (<2 GHz) spectrum of the northern relic is well represented by a power law, it clearly steepens towards 16 GHz. This result is inconsistent with diffusive shock acceleration predictions of ageing plasma behind a uniform shock front. The steepening could be caused by an inhomogeneous medium with temperature/density gradients or by lower acceleration efficiencies of high energy electrons. Further modelling is necessary to explain the observed spectrum.Peer reviewe

Marine environmental DNA biomonitoring reveals seasonal patterns in biodiversity and identifies ecosystem responses to anomalous climatic events

Marine ecosystems are changing rapidly as the oceans warm and become more acidic. The physical factors and the changes to ocean chemistry that they drive can all be measured with great precision. Changes in the biological composition of communities in different ocean regions are far more challenging to measure because most biological monitoring methods focus on a limited taxonomic or size range. Environmental DNA (eDNA) analysis has the potential to solve this problem in biological oceanography, as it is capable of identifying a huge phylogenetic range of organisms to species level. Here we develop and apply a novel multi-gene molecular toolkit to eDNA isolated from bulk plankton samples collected over a five-year period from a single site. This temporal scale and level of detail is unprecedented in eDNA studies. We identified consistent seasonal assemblages of zooplankton species, which demonstrates the ability of our toolkit to audit community composition. We were also able to detect clear departures from the regular seasonal patterns that occurred during an extreme marine heatwave. The integration of eDNA analyses with existing biotic and abiotic surveys delivers a powerful new long-term approach to monitoring the health of our world's oceans in the context of a rapidly changing climate

First results from the Very Small Array -- IV. Cosmological parameter estimation

We investigate the constraints on basic cosmological parameters set by the first compact-configuration observations of the Very Small Array (VSA), and other cosmological data sets, in the standard inflationary LambdaCDM model. Using a weak prior 40 < H_0 < 90 km/s/Mpc and 0 < tau < 0.5 we find that the VSA and COBE_DMR data alone produce the constraints Omega_tot = 1.03^{+0.12}_{-0.12}, Omega_bh^2 = 0.029^{+0.009}_{-0.009}, Omega_cdm h^2 = 0.13^{+0.08}_{-0.05} and n_s = 1.04^{+0.11}_{-0.08} at the 68 per cent confidence level. Adding in the type Ia supernovae constraints, we additionally find Omega_m = 0.32^{+0.09}_{-0.06} and Omega_Lambda = 0.71^{+0.07}_{-0.07}. These constraints are consistent with those found by the BOOMERanG, DASI and MAXIMA experiments. We also find that, by combining all the recent CMB experiments and assuming the HST key project limits for H_0 (for which the X-ray plus Sunyaev--Zel'dovich route gives a similar result), we obtain the tight constraints Omega_m=0.28^{+0.14}_{-0.07} and Omega_Lambda= 0.72^{+0.07}_{-0.13}, which are consistent with, but independent of, those obtained using the supernovae data.Comment: 10 pages, 6 figures, MNRAS in pres

Cosmological parameter estimation using Very Small Array data out to ℓ= 1500

We estimate cosmological parameters using data obtained by the Very Small Array (VSA) in its extended configuration, in conjunction with a variety of other cosmic microwave background (CMB) data and external priors. Within the flat Λ cold dark matter (ΛCDM) model, we find that the inclusion of high-resolution data from the VSA modifies the limits on the cosmological parameters as compared to those suggested by the Wilkinson Microwave Anisotropy Probe (WMAP) alone, while still remaining compatible with their estimates. We find that Ωbh2= 0.0234+0.0012−0.0014, Ωdmh2= 0.111+0.014−0.016, h= 0.73+0.09−0.05, nS= 0.97+0.06−0.03, 1010AS= 23+7−3 and τ= 0.14+0.14−0.07 for WMAP and VSA when no external prior is included. On extending the model to include a running spectral index of density fluctuations, we find that the inclusion of VSA data leads to a negative running at a level of more than 95 per cent confidence ( nrun=−0.069 ± 0.032 ), something that is not significantly changed by the inclusion of a stringent prior on the Hubble constant. Inclusion of prior information from the 2dF galaxy redshift survey reduces the significance of the result by constraining the value of Ωm. We discuss the veracity of this result in the context of various systematic effects and also a broken spectral index model. We also constrain the fraction of neutrinos and find that fν < 0.087 at 95 per cent confidence, which corresponds to mν < 0.32 eV when all neutrino masses are equal. Finally, we consider the global best fit within a general cosmological model with 12 parameters and find consistency with other analyses available in the literature. The evidence for nrun < 0 is only marginal within this model

A VSA search for the extended Sunyaev-Zel'dovich Effect in the Corona Borealis Supercluster

We present interferometric imaging at 33 GHz of the Corona Borealis supercluster, using the extended configuration of the Very Small Array. A total area of 24 deg^2 has been imaged, with an angular resolution of 11 arcmin and a sensitivity of 12 mJy/beam. The aim of these observations is to search for Sunyaev-Zel'dovich (SZ) detections from known clusters of galaxies in this supercluster and for a possible extended SZ decrement due to diffuse warm/hot gas in the intercluster medium. We measure negative flux values in the positions of the ten richest clusters in the region. Collectively, this implies a 3.0-sigma detection of the SZ effect. In the clusters A2061 and A2065 we find decrements of approximately 2-sigma. Our main result is the detection of two strong and resolved negative features at -70+-12 mJy/beam (-157+-27 microK) and -103+-10 mJy/beam (-230+-23 microK), respectively, located in a region with no known clusters, near the centre of the supercluster. We discuss their possible origins in terms of primordial CMB anisotropies and/or SZ signals related to either unknown clusters or to a diffuse extended warm/hot gas distribution. Our analyses have revealed that a primordial CMB fluctuation is a plausible explanation for the weaker feature (probability of 37.82%). For the stronger one, neither primordial CMB (probability of 0.33%) nor SZ can account alone for its size and total intensity. The most reasonable explanation, then, is a combination of both primordial CMB and SZ signal. Finally, we explore what characteristics would be required for a filamentary structure consisting of warm/hot diffuse gas in order to produce a significant contribution to such a spot taking into account the constraints set by X-ray data.Comment: 16 pages, 10 figures. Accepted in MNRA

Microwave observations of spinning dust emission in NGC6946

We report new cm-wave measurements at five frequencies between 15 and 18GHz of the continuum emission from the reportedly anomalous "region 4" of the nearby galaxy NGC6946. We find that the emission in this frequency range is significantly in excess of that measured at 8.5GHz, but has a spectrum from 15-18GHz consistent with optically thin free-free emission from a compact HII region. In combination with previously published data we fit four emission models containing different continuum components using the Bayesian spectrum analysis package radiospec. These fits show that, in combination with data at other frequencies, a model with a spinning dust component is slightly preferred to those that possess better-established emission mechanisms.Comment: submitted MNRA

Looking for big 'fry': the motives and methods of middle-class international property investors

Anxieties about the effects of international property investment in world cities like London have mainly focused on super-rich investors and corporate vehicles that have generated price inflation of assets and accelerated exclusion from an already expensive market. In fact, many international investors in the city’s housing market are middle-class individuals, and focusing on Hong Kong as an emblematic example of such processes, we examine their motives and the products offered to them by important investment intermediaries. We find that an important rationale for these investments lies in local class-based uncertainties and existential anxieties concerning the future of Hong Kong itself. We focus on the cultural roots of these investor rationalities but also consider the role of investment intermediaries who have helped bolster confidence while shielding investors from the consequences of their aggregated market power - concerns in London over household displacement from foreign investment. We suggest that what may seem to be the predatory search to ‘fry’ property (炒樓), a Hongkonger colloquialism referring to the search for high performing investments, should also be understood as actions anchored in and generated by the habitus of the Hong Kong middle-class whose lives have been moulded by historical geopolitical uncertainty and worries about its longer-term social positioning and security

Multifrequency spectral analysis of extragalactic radio sources in the 33-GHz VSA catalogue: sources with flattening and upturn spectrum

We present an analysis of the spectral properties of the extragalactic radio sources in the nearly complete Very Small Array (VSA) sample at 33 GHz. Data from different surveys are used to study source spectra between 1.4 and 33 GHz. We find that, in general, spectra cannot be well described by a single power law in the range of frequencies considered. In particular, most of the VSA sources that are steep between 1.4 and 5 GHz, show a spectral flattening at ν > 5 GHz. We identify 20 objects (19 per cent of the sample) clearly characterized by an upturn spectrum, i.e. a spectrum falling at low frequencies (ν less than or similar to 5 GHz) and inverted at higher frequencies. Spectra with high-frequency flattening or upturn shape are supposed to occur when the emission from the active galactic nucleus (AGN) compact core begins to dominate over the component from extended lobes. This picture fits well with the AGN unified scheme, for objects observed at intermediate viewing angles of the AGN jet. Finally, we discuss implications that this class of sources can have on future cosmic microwave background observations at high resolution