Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes

Preterm birth is a major risk factor for neurodevelopmental delays and disorders. This study aimed to identify genomic biomarkers of intrauterine inflammation in umbilical cord tissue in preterm neonates that predict cognitive impairment at 10 years of age

Characterization of the three Arabidopsis thaliana RAD21 cohesins reveals differential responses to ionizing radiation

The RAD21/REC8 gene family has been implicated in sister chromatid cohesion and DNA repair in several organisms. Unlike most eukaryotes, Arabidopsis thaliana has three RAD21 gene homologues, and their cloning and characterization are reported here. All three genes, AtRAD21.1, AtRAD21.2, and AtRAD21.3, are expressed in tissues rich in cells undergoing cell division, and AtRAD21.3 shows the highest relative level of expression. An increase in steady-state levels of AtRAD21.1 transcript was also observed, specifically after the induction of DNA damage. Phenotypic analysis of the atrad21.1 and atrad21.3 mutants revealed that neither of the single mutants was lethal, probably due to the redundancy in function of the AtRAD21 genes. However, AtRAD21.1 plays a critical role in recovery from DNA damage during seed imbibition, prior to germination, as atrad21.1 mutant seeds are hypersensitive to radiation damag

First evaluation of the feasibility of MLC tracking using ultrasound motion estimation.

Purpose To quantify the performance of the Clarity ultrasound (US) imaging system (Elekta AB, Stockholm, Sweden) for real-time dynamic multileaf collimator (MLC) tracking.Methods The Clarity calibration and quality assurance phantom was mounted on a motion platform moving with a periodic sine wave trajectory. The detected position of a 30 mm hypoechogenic sphere within the phantom was continuously reported via Clarity's real-time streaming interface to an in-house tracking and delivery software and subsequently used to adapt the MLC aperture. A portal imager measured MV treatment field/MLC apertures and motion platform positions throughout each experiment to independently quantify system latency and geometric error. Based on the measured range of latency values, a prostate stereotactic body radiation therapy (SBRT) delivery was performed with three realistic motion trajectories. The dosimetric impact of system latency on MLC tracking was directly measured using a 3D dosimeter mounted on the motion platform.Results For 2D US imaging, the overall system latency, including all delay times from the imaging and delivery chain, ranged from 392 to 424 ms depending on the lateral sector size. For 3D US imaging, the latency ranged from 566 to 1031 ms depending on the elevational sweep. The latency-corrected geometric root-mean squared error was below 0.75 mm (2D US) and below 1.75 mm (3D US). For the prostate SBRT delivery, the impact of a range of system latencies (400-1000 ms) on the MLC tracking performance was minimal in terms of gamma failure rate.Conclusions Real-time MLC tracking based on a noninvasive US input is technologically feasible. Current system latencies are higher than those for x-ray imaging systems, but US can provide full volumetric image data and the impact of system latency was measured to be small for a prostate SBRT case when using a US-like motion input

Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life

Abstract: Background The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to impact placental function, fetal development and child health later in life. Study design Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from extremely preterm births (EPTBs) (n = 84). The association between the identified differentially methylated CpG sites and neurocognitive outcome at ten years of age was then evaluated. Results Spontaneous EPTB was associated with differential CpG methylation levels in 250 CpG sites (217 unique genes) with the majority displaying hypermethylation. The identified genes are known to play a role in neurodevelopment and are enriched for basic helix-loop-helix transcription factor binding sites. The placental CpG methylation levels for 17 of these sites predicted cognitive function at ten years of age. Conclusion A hypermethylation signature is present in DNA from placentas in infants with spontaneous EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted..

The Formation of Population III Binaries from Cosmological Initial Conditions

Previous high resolution cosmological simulations predict the first stars to appear in the early universe to be very massive and to form in isolation. Here we discuss a cosmological simulation in which the central 50M{sub {circle_dot}} clump breaks up into two cores, having a mass ratio of two to one, with one fragment collapsing to densities of 10{sup -8}g cm{sup -3}. The second fragment, at a distance of {approx}800 astronomical units, is also optically thick to its own cooling radiation from molecular hydrogen lines, but is still able to cool via collision-induced emission. The two dense peaks will continue to accrete from the surrounding cold gas reservoir over a period of {approx} 10{sup 5} years and will likely form a binary star system

Dark Matter Halo Environment for Primordial Star Formation

We study the statistical properties (such as shape and spin) of high-z halos likely hosting the first (PopIII) stars with cosmological simulations including detailed gas physics. In the redshift range considered ($11 < z < 16$) the average sphericity is $= 0.3 \pm 0.1$, and for more than 90% of halos the triaxiality parameter is $T \lesssim 0.4$, showing a clear preference for oblateness over prolateness. Larger halos in the simulation tend to be both more spherical and prolate: we find $s \propto M_h^{\alpha_s}$ and $T \propto M_h^{\alpha_T}$, with $\alpha_s \approx 0.128$ and $\alpha_T= 0.276$ at z = 11. The spin distributions of dark matter and gas are considerably different at $z=16$, with the baryons rotating slower than the dark matter. At lower redshift, instead, the spin distributions of dark matter and gas track each other almost perfectly, as a consequence of a longer time interval available for momentum redistribution between the two components. The spin of both the gas and dark matter follows a lognormal distribution, with a mean value at z=16 of $=0.0184$, virtually independent of halo mass. This is in good agreement with previous studies. Using the results of two feedback models (MT1 and MT2) by McKee & Tan (2008) and mapping our halo spin distribution into a PopIII IMF, we find that at high-$z$ the IMF closely tracks the spin lognormal distribution. Depending on the feedback model, though, the distribution can be centered at $\approx 65 M_\odot$ (MT1) or $\approx 140 M_\odot$ (MT2). At later times, model MT1 evolves into a bimodal distribution with a second prominent peak located at $35-40 M_\odot$ as a result of the non-linear relation between rotation and halo mass. We conclude that the dark matter halo properties might be a key factor shaping the IMF of the first stars.Comment: 10 pages, 6 figures, accepted for publication in MNRA

Identification of potential “Remedies” for Air Pollution (nitrogen) Impacts on Designated Sites (RAPIDS)

Atmospheric nitrogen (N) deposition is a significant threat to semi-natural habitats and species in the UK, resulting in on-going erosion of habitat quality and declines in many species of high conservation value. The project focused on impacts and remedies for designated conservation sites, especially Natura 2000 sites protected under the EU Habitats Directive. However, the approach and certainly the measures could be equally applied to other areas of high conservation value. Evidence was drawn together to develop a framework for identifying key N threats at individual sites as a basis to target mitigation options in the context of potential legislative, voluntary and financial instruments

Generation of cardiomyocytes from human-induced pluripotent stem cells resembling atrial cells with ability to respond to adrenoceptor agonists

Atrial fibrillation (AF) is the most common chronic arrhythmia presenting a heavy disease burden. We report a new approach for generating cardiomyocytes (CMs) resembling atrial cells from human-induced pluripotent stem cells (hiPSCs) using a combination of Gremlin 2 and retinoic acid treatment. More than 40% of myocytes showed rod-shaped morphology, expression of CM proteins (including ryanodine receptor 2, α-actinin-2 and F-actin) and striated appearance, all of which were broadly similar to the characteristics of adult atrial myocytes (AMs). Isolated myocytes were electrically quiescent until stimulated to fire action potentials with an AM profile and an amplitude of approximately 100 mV, arising from a resting potential of approximately −70 mV. Single-cell RNA sequence analysis showed a high level of expression of several atrial-specific transcripts including NPPA, MYL7, HOXA3, SLN, KCNJ4, KCNJ5 and KCNA5. Amplitudes of calcium transients recorded from spontaneously beating cultures were increased by the stimulation of α-adrenoceptors (activated by phenylephrine and blocked by prazosin) or β-adrenoceptors (activated by isoproterenol and blocked by CGP20712A). Our new approach provides human AMs with mature characteristics from hiPSCs which will facilitate drug discovery by enabling the study of human atrial cell signalling pathways and AF. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’

Breaking the Attosecond, Angstrom and TV/M Field Barriers with Ultra-Fast Electron Beams

Recent initiatives at UCLA concerning ultra-short, GeV electron beam generation have been aimed at achieving sub-fs pulses capable of driving X-ray free-electron lasers (FELs) in single-spike mode. This use of very low Q beams may allow existing FEL injectors to produce few-100 attosecond pulses, with very high brightness. Towards this end, recent experiments at the LCLS have produced {approx}2 fs, 20 pC electron pulses. We discuss here extensions of this work, in which we seek to exploit the beam brightness in FELs, in tandem with new developments in cryogenic undulator technology, to create compact accelerator-undulator systems that can lase below 0.15 {angstrom}, or be used to permit 1.5 {angstrom} operation at 4.5 GeV. In addition, we are now developing experiments which use the present LCLS fs pulses to excite plasma wakefields exceeding 1 TV/m, permitting a table-top TeV accelerator for frontier high energy physics applications

On the Role of Attention in Binocular Rivalry: Electrophysiological Evidence

During binocular rivalry visual consciousness fluctuates between two dissimilar monocular images. We investigated the role of attention in this phenomenon by comparing event-related potentials (ERPs) when binocular-rivalry stimuli were attended with when they were unattended. Stimuli were dichoptic, orthogonal gratings that yielded binocular rivalry and dioptic, identically oriented gratings that yielded binocular fusion. Events were all possible orthogonal changes in orientation of one or both gratings. We had two attention conditions: In the attend-to-grating condition, participants had to report changes in perceived orientation, focussing their attention on the gratings. In the attend-to-fixation condition participants had to report changes in a central fixation target, taking attention away from the gratings. We found, surprisingly, that attending to rival gratings yielded a smaller ERP component (the N1, from 160–210 ms) than attending to the fixation target. To explain this paradoxical effect of attention, we propose that rivalry occurs in the attend-to-fixation condition (we found an ERP signature of rivalry in the form of a sustained negativity from 210–300 ms) but that the mechanism processing the stimulus changes is more adapted in the attend-to-grating condition than in the attend-to-fixation condition. This is consistent with the theory that adaptation gives rise to changes of visual consciousness during binocular rivalry