Statin regulated ERK5 stimulates tight junction formation and reduces permeability in human cardiac endothelial cells

The MEKK3/MEK5/ERK5 signaling axis is required for cardiovascular development in vivo. We analyzed the physiological role of ERK5 in cardiac endothelial cells and the consequence of activation of this kinase by the statin class of HMG Co‐A reductase inhibitor drugs. We utilized human cardiac microvascular endothelial cells (HCMECs) and altered ERK5 expression using siRNA mediated gene silencing or overexpression of constitutively active MEK5 and ERK5 to reveal a role for ERK5 in regulating endothelial tight junction formation and cell permeability. Statin treatment of HCMECs stimulated activation of ERK5 and translocation to the plasma membrane resulting in co‐localization with the tight junction protein ZO‐1 and a concomitant reduction in endothelial cell permeability. Statin mediated activation of ERK5 was a consequence of reduced isoprenoid synthesis following HMG Co‐A reductase inhibition. Statin pretreatment could overcome the effect of doxorubicin in reducing endothelial tight junction formation and prevent increased permeability. Our data provide the first evidence for the role of ERK5 in regulating endothelial tight junction formation and endothelial cell permeability. Statin mediated ERK5 activation and the resulting decrease in cardiac endothelial cell permeability may contribute to the cardioprotective effects of statins in reducing doxorubicin‐induced cardiotoxicity

Timeseries partitioning of ecosystem respiration components in seasonal, non-tropical forests; comparing literature derived coefficients with evaluation at two contrasting UK forest sites

Funding The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by UK Research and Innovation and the Biotechnology and Biological Research Council through the Strategic Priorities Fund for Greenhouse Gas Removal. NetZeroPlus: Sustainable Treescapes Demonstrator and Decision Tools (Netzeroplus.ac.uk), Grant number BB/V011588/1. The Alice Holt 2010 soil flux data were collected as part of a Natural Environment Research Council (NERC grants: F14/G6/105 & NE/C513550/1) funded project Centre for Terrestrial Carbon Dynamics. Acknowledgments The authors would like to thank Prof. Jo Smith at Aberdeen University for comments and suggestions on an early draft, and special thanks to Edward Eaton for assisting with running the Alice Holt site and contributing to the soil flux measurements. We are further grateful to the Forestry Commission, UK, for funding both the Alice Holt and Harwood long-term research sites.Peer reviewe

Porphyrin dyes for nonlinear optical imaging of live cells

Second harmonic generation (SHG)-based probes are useful for nonlinear optical imaging of biological structures, such as the plasma membrane. Several amphiphilic porphyrin-based dyes with high SHG coefficients have been synthesized with different hydrophilic head groups, and their cellular targeting has been studied. The probes with cationic head groups localize better at the plasma membrane than the neutral probes with zwitterionic or non-charged ethylene glycol-based head groups. Porphyrin dyes with only dications as hydrophilic head groups localize inside HEK293T cells to give SHG, whereas tricationic dyes localize robustly at the plasma membrane of cells, including neurons, in vitro and ex vivo. The copper(II) complex of the tricationic dye with negligible fluorescence quantum yield works as an SHG-only dye. The free-base tricationic dye has been demonstrated for two-photon fluorescence and SHG-based multimodal imaging. This study demonstrates the importance of a balance between the hydrophobicity and hydrophilicity of amphiphilic dyes for effective plasma membrane localization

Combined electrical resistivity tomography and ground penetrating radar to map Eurasian badger (Meles Meles) burrows in clay-rich flood embankments (levees)

Globally, earth embankments are used to protect against flooding. Raised above the surrounding water table, these embankments make ideal habitats for many burrowing animals whose burrows can impact their structural integrity. Ground Penetrating Radar (GPR) is commonly used to identify and map animal burrows and other small cavities. However, the depth of investigation of a GPR survey can be severely limited in saline and clay-rich environments, soil properties commonly associated with flood embankments. In contrast, Electrical Resistivity Tomography (ERT) can image subsurface voids in conductive ground conditions but has been rarely used to image animal burrows. Here we aim to assess the efficacy of ERT and GPR to image two badger burrow networks, called ‘setts’, located in clay embankments on the River Ouse, Yorkshire, UK. The two setts were excavated to validate the geophysical results, and the soil was characterised through logging and geotechnical analysis to develop a ground model of the site. We find that ERT can accurately resolve tunnels down to 1.5 m depth, map the structure of a multi-entrance badger sett and successfully identify the end of the tunnels. This result compares favourably to the GPR surveys, which mapped all but the deepest tunnels, limited by its penetration depth due to clay soils. Our results show that ERT can be used as a primary survey tool for animal burrows in clay-rich environments and can be validated using co-located GPR surveys if penetration depth is sufficient. The implications of this study may allow embankment managers to map burrow networks, assess flood embankment stability, minimise repair costs, and reduce unexpected failures during flood events. Additionally, a better understanding of how, for example, local heterogeneities impact badgers' burrow geometry may be achievable using these geophysical methods, as they provide a non-destructive, repeatable method for imaging setts

Emerging Technologies and Approaches for In Situ, Autonomous Observing in the Arctic

Understanding and predicting Arctic change and its impacts on global climate requires broad, sustained observations of the atmosphere-ice-ocean system, yet technological and logistical challenges severely restrict the temporal and spatial scope of observing efforts. Satellite remote sensing provides unprecedented, pan-Arctic measurements of the surface, but complementary in situ observations are required to complete the picture. Over the past few decades, a diverse range of autonomous platforms have been developed to make broad, sustained observations of the ice-free ocean, often with near-real-time data delivery. Though these technologies are well suited to the difficult environmental conditions and remote logistics that complicate Arctic observing, they face a suite of additional challenges, such as limited access to satellite services that make geolocation and communication possible. This paper reviews new platform and sensor developments, adaptations of mature technologies, and approaches for their use, placed within the framework of Arctic Ocean observing needs

Optical Structure and Proper-Motion Age of the Oxygen-rich Supernova Remnant 1E 0102-7219 in the Small Magellanic Cloud

We present new optical emission-line images of the young SNR 1E 0102-7219 (E0102) in the SMC obtained with the HST Advanced Camera for Surveys (ACS). E0102 is a member of the oxygen-rich class of SNRs showing strong oxygen, neon , and other metal-line emissions in its optical and X-ray spectra, and an absence of H and He. The progenitor of E0102 may have been a Wolf-Rayet star that underwent considerable mass loss prior to exploding as a Type Ib/c or IIL/b SN. The ejecta in this SNR are fast-moving (V > 1000 km/s) and emit as they are compressed and heated in the reverse shock. In 2003, we obtained optical [O III], H-alpha, and continuum images with the ACS Wide Field Camera. The [O III] image captures the full velocity range of the ejecta, and shows considerable high-velocity emission projected in the middle of the SNR that was Doppler-shifted out of the narrow F502N bandpass of a previous Wide Field and Planetary Camera 2 image from 1995. Using these two epochs separated by ~8.5 years, we measure the transverse expansion of the ejecta around the outer rim in this SNR for the first time at visible wavelengths. From proper-motion measurements of 12 ejecta filaments, we estimate a mean expansion velocity for the bright ejecta of ~2000 km/s and an inferred kinematic age for the SNR of \~2050 +/- 600 years. The age we derive from HST data is about twice that inferred by Hughes et al.(2000) from X-ray data, though our 1-sigma error bars overlap. Our proper-motion age is consistent with an independent optical kinematic age derived by Eriksen et al.(2003) using spatially resolved [O III] radial-velocity data. We derive an expansion center that lies very close to X-ray and radio hotspots, which could indicate the presence of a compact remnant (neutron star or black hole).Comment: 28 pages, 8 figures. Accepted to the Astrophysical Journal, to appear in 20 April 2006 issue. Full resolution figures are posted at: http://stevenf.asu.edu/figure

MicroEnv: A microsimulation model for quantifying the impacts of environmental policies on population health and health inequalities.

The Sustainable Development Goals (SDGs) recognise the critical need to improve population health and environmental sustainability. This paper describes the development of a microsimulation model, MicroEnv, aimed at quantifying the impact of environmental exposures on health as an aid to selecting policies likely to have greatest benefit. Its methods allow the integration of morbidity and mortality outcomes and the generation of results at high spatial resolution. We illustrate its application to the assessment of the impact of air pollution on health in London. Simulations are performed at Lower Layer Super Output Area (LSOA), the smallest geographic unit (population of around 1500 inhabitants) for which detailed socio-demographic data are routinely available in the UK. The health of each individual in these LSOAs is simulated year-by-year using a health-state-transition model, where transition probabilities from one state to another are based on published statistics modified by relative risks that reflect the effect of environmental exposures. This is done through linkage of the simulated population in each LSOA with 1?×?1 km annual average PM2.5 concentrations and area-based deprivation indices. Air pollution is a leading cause of mortality and morbidity globally, and improving air quality is critical to the SDGs for Health (Goal 3) and Cities (Goal 11). The evidence of MicroEnv is aimed at providing better understanding of the benefits for population health and health inequalities of policy actions that affect exposure such as air quality, and thus to help shape policy decisions. Future work will extend the model to integrate other environmental determinants of health

Production of haploids and doubled haploids in oil palm

Background: Oil palm is the world’s most productive oil-food crop despite yielding well below its theoretical maximum. This maximum could be approached with the introduction of elite F1 varieties. The development of such elite lines has thus far been prevented by difficulties in generating homozygous parental types for F1 generation. Results: Here we present the first high-throughput screen to identify spontaneously-formed haploid (H) and doubled haploid (DH) palms. We secured over 1,000 Hs and one DH from genetically diverse material and derived further DH/mixoploid palms from Hs using colchicine. We demonstrated viability of pollen from H plants and expect to generate 100% homogeneous F1 seed from intercrosses between DH/mixoploids once they develop female inflorescences. Conclusions: This study has generated genetically diverse H/DH palms from which parental clones can be selected in sufficient numbers to enable the commercial-scale breeding of F1 varieties. The anticipated step increase in productivity may help to relieve pressure to extend palm cultivation, and limit further expansion into biodiverse rainforest

Time-sequenced Multi-Radio-Frequency Observations of Cygnus X-3 in Flare

Multifrequency observations from the VLA, VLBA and OVRO Millimeter Array of a major radio outburst of Cygnus X-3 in 2001 September are presented, measuring the evolution of the spectrum of the source over three decades in frequency, over a period of six days. Following the peak of the flare, as the intensity declines the high-frequency spectrum at frequency nu steepens from nu^{-0.4} to nu^{-0.6}, after which the spectral index remains at this latter terminal value; a trend previously observed but hitherto not satisfactorily explained. VLBA observations, for the first time, track over several days the expansion of a sequence of knots whose initial diameters are approximately 8 milliarcseconds. The light-crossing time within these plasmons is of the same order as the time-scale over which the spectrum is observed to evolve. We contend that properly accounting for light-travel time effects in and between plasmons which are initially optically thick, but which after expansion become optically thin, explains the key features of the spectral evolution, for example the observed timescale. Using the VLBA images, we have directly measured for the first time the proper motions of individual knots, analysis of which shows a two-sided jet whose axis is precessing. The best-fit jet speed is roughly beta = 0.63 and the precession period is about 5 days, significantly lower than fitted for a previous flare. Extrapolation of the positions of the knots measured by the VLBA back to zero-separation shows this to occur approximately 2.5 days after the detection of the rise in flux density of Cygnus X-3.Comment: 23 pages, 10 figures, accepted by Ap