Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families

The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins

Anatomy-Aware Self-supervised Fetal MRI Synthesis from Unpaired Ultrasound Images

Fetal brain magnetic resonance imaging (MRI) offers exquisite images of the developing brain but is not suitable for anomaly screening. For this ultrasound (US) is employed. While expert sonographers are adept at reading US images, MR images are much easier for non-experts to interpret. Hence in this paper we seek to produce images with MRI-like appearance directly from clinical US images. Our own clinical motivation is to seek a way to communicate US findings to patients or clinical professionals unfamiliar with US, but in medical image analysis such a capability is potentially useful, for instance, for US-MRI registration or fusion. Our model is self-supervised and end-to-end trainable. Specifically, based on an assumption that the US and MRI data share a similar anatomical latent space, we first utilise an extractor to determine shared latent features, which are then used for data synthesis. Since paired data was unavailable for our study (and rare in practice), we propose to enforce the distributions to be similar instead of employing pixel-wise constraints, by adversarial learning in both the image domain and latent space. Furthermore, we propose an adversarial structural constraint to regularise the anatomical structures between the two modalities during the synthesis. A cross-modal attention scheme is proposed to leverage non-local spatial correlations. The feasibility of the approach to produce realistic looking MR images is demonstrated quantitatively and with a qualitative evaluation compared to real fetal MR images.Comment: MICCAI-MLMI 201

Charge Symmetry Breaking in dd->4He{\pi}0 with WASA-at-COSY

Charge symmetry breaking (CSB) observables are a suitable experimental tool to examine effects induced by quark masses on the nuclear level. Previous high precision data from TRIUMF and IUCF are currently used to develop a consistent description of CSB within the framework of chiral perturbation theory. In this work the experimental studies on the reaction dd->4He{\pi}0 have been extended towards higher excess energies in order to provide information on the contribution of p-waves in the final state. For this, an exclusive measurement has been carried out at a beam momentum of p=1.2 GeV/c using the WASA-at-COSY facility. The total cross section amounts to sigma(tot) = (118 +- 18(stat) +- 13(sys) +- 8(ext)) pb and first data on the differential cross section are consistent with s-wave pion production.Comment: 14 pages, 5 figure

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

Cross section ratio and angular distributions of the reaction p + d -> 3He + eta at 48.8 MeV and 59.8 MeV excess energy

We present new data for angular distributions and on the cross section ratio of the p + d -> 3He + eta reaction at excess energies of Q = 48.8 MeV and Q = 59.8 MeV. The data have been obtained at the WASA-at-COSY experiment (Forschungszentrum J\"ulich) using a proton beam and a deuterium pellet target. While the shape of obtained angular distributions show only a slow variation with the energy, the new results indicate a distinct and unexpected total cross section fluctuation between Q = 20 MeV and Q = 60 MeV, which might indicate the variation of the production mechanism within this energy interval.Comment: 9 pages, 9 figure

Is the beck anxiety inventory a good tool to assess the severity of anxiety? A primary care study in The Netherlands study of depression and anxiety (NESDA)

<p>Abstract</p> <p>Background</p> <p>Appropriate management of anxiety disorders in primary care requires clinical assessment and monitoring of the severity of the anxiety. This study focuses on the Beck Anxiety Inventory (BAI) as a severity indicator for anxiety in primary care patients with different anxiety disorders (social phobia, panic disorder with or without agoraphobia, agoraphobia or generalized anxiety disorder), depressive disorders or no disorder (controls).</p> <p>Methods</p> <p>Participants were 1601 primary care patients participating in the Netherlands Study of Depression and Anxiety (NESDA). Regression analyses were used to compare the mean BAI scores of the different diagnostic groups and to correct for age and gender.</p> <p>Results</p> <p>Patients with any anxiety disorder had a significantly higher mean score than the controls. A significantly higher score was found for patients with panic disorder and agoraphobia compared to patients with agoraphobia only or social phobia only. BAI scores in patients with an anxiety disorder with a co-morbid anxiety disorder and in patients with an anxiety disorder with a co-morbid depressive disorder were significantly higher than BAI scores in patients with an anxiety disorder alone or patients with a depressive disorder alone. Depressed and anxious patients did not differ significantly in their mean scores.</p> <p>Conclusions</p> <p>The results suggest that the BAI may be used as a severity indicator of anxiety in primary care patients with different anxiety disorders. However, because the instrument seems to reflect the severity of depression as well, it is not a suitable instrument to discriminate between anxiety and depression in a primary care population.</p

Search for a dark photon in the π0→e+e−γ\pi^0 \to e^+e^-\gamma decay

The presently world largest data sample of pi0 --> gamma e+e- decays containing nearly 5E5 events was collected using the WASA detector at COSY. A search for a dark photon U produced in the pi0 --> gamma U --> gamma e+e- decay from the pp-->pp\pi^0 reaction was carried out. An upper limit on the square of the U-gamma mixing strength parameter epsilon^2 of 5e-6 at 90% CL was obtained for the mass range 20 MeV <M_U< 100 MeV. This result together with other recent experimental limits significantly reduces the M_U vs. \epsilon^2 parameter space preferred by the measured value of the muon anomalous magnetic moment.Comment: 16 pages, 8 figures; improved analysis extending the exclusion region to 20 MeV<M_U< 100 MeV; implemented changes requested by referee

Species' geographic distributions through time: Playing catchup with changing climates

This is the author's accepted manuscript.Species’ ranges are often treated as a rather fixed characteristic, rather than a fluid, ever-changing manifestation of their ecological requirements and dispersal abilities. Paleontologists generally have had a more flexible point of view on this issue than neontologists, but each perspective can improve by appreciating the other. Here, we provide an overview of paleontological and neontological perspectives on species’ geographic distributions, focusing on what can be learned about historical variations in distributions. The cross-disciplinary view, we hope, offers some novel perspectives on species-level biogeography

ABC Effect in Basic Double-Pionic Fusion --- Observation of a new resonance?

We report on a high-statistics measurement of the basic double pionic fusion reaction $pn \to d\pi^0\pi^0$ over the energy region of the so-called ABC effect, a pronounced low-mass enhancement in the $\pi\pi$-invariant mass spectrum. The measurements were performed with the WASA detector setup at COSY. The data reveal the ABC effect to be associated with a Lorentzian shaped energy dependence in the integral cross section. The observables are consistent with a resonance with $I(J^P) =0(3^+)$ in both $pn$ and $\Delta\Delta$ systems. Necessary further tests of the resonance interpretation are discussed

Broad and narrow personality traits as markers of one-time and repeated suicide attempts: A population-based study

<p>Abstract</p> <p>Background</p> <p>Studying personality traits with the potential to differentiate between individuals engaging in suicide attempts of different degrees of severity could help us to understand the processes underlying the link of personality and nonfatal suicidal behaviours and to identify at-risk groups. One approach may be to examine whether narrow, i.e., lower-order personality traits may be more useful than their underlying, broad personality trait dimensions.</p> <p>Methods</p> <p>We investigated qualitative and quantitative differences in broad and narrow personality traits between one-time and repeated suicide attempters in a longitudinal, population-based sample of young French Canadian adults using two multivariate regression models.</p> <p>Results</p> <p>One broad (Compulsivity: OR = 2.0; 95% CI 1.2–3.5) and one narrow personality trait (anxiousness: OR = 1.1; 95% CI 1.01–1.1) differentiated between individuals with histories of repeated and one-time suicide attempts. Affective instability [(OR = 1.1; 95% CI 1.04–1.1)] and anxiousness [(OR = .92; 95% CI .88–.95)], on the other hand, differentiated between nonattempters and one-time suicide attempters.</p> <p>Conclusion</p> <p>Emotional and cognitive dysregulation and associated behavioural manifestations may be associated with suicide attempts of different severity. While findings associated with narrow traits may be easier to interpret and link to existing sociobiological theories, larger effect sizes associated with broad traits such as Compulsivity may be better suited to objectives with a more clinical focus.</p