Environmental manipulations generate bidirectional shifts in both behavior and gene regulation in a crossbred mouse model of extremes in trait anxiety

Although gene-environment interactions are known to significantly influence psychopathology related disease states, only few animal models cover both the genetic background and environmental manipulations. Therefore, we have taken advantage of the bidirectionally inbred high (HAB) and low (LAB) anxiety-related behavior mouse lines to generate HAB x LAB F1 hybrids that intrinsically carry both lines' genetic characteristics, and subsequently raised them in three different environments standard, enriched (EE) and chronic mild stress (CMS). Assessing genetic correlates of trait anxiety, we focused on two genes already known to play a role in HAB vs. LAB mice, corticotropin releasing hormone receptor type 1 (Crhr1) and high mobility group nucleosomal binding domain 3 (Hmgn3). While EE F1 mice showed decreased anxiety related and increased explorative behaviors compared to controls, CMS sparked effects in the opposite direction. However, environmental treatments affected the expression of the two genes in distinct ways. Thus, while expression ratios of Hmgn3 between the HAB- and LAB-specific alleles remained equal, total expression resembled the one observed in HAB vs. LAB mice, i.e., decreased after EE and increased after CMS treatment. On the other hand, while total expression of Crhr1 remained unchanged between the groups, the relative expression of HAB- and LAB-specific alleles showed a clear effect following the environmental modifications. Thus, the environmentally driven bidirectional shift of trait anxiety in this F1 model strongly correlated with Hmgn3 expression, irrespective of allele-specific expression patterns that retained the proportions of basic differential HAB vs. LAB expression, making this gene a match for environment-induced modifications. An involvement of Crhr1 in the bidirectional behavioral shift could, however, rather be due to different effects of the HAB- and LAB specific alleles described here. Both candidate genes therefore deserve attention in the complex regulation of anxiety-related phenotypes including environment-mediated effects

Mission design for LISA Pathfinder

Here we describe the mission design for SMART-2/LISA Pathfinder. The best trade-off between the requirements of a low-disturbance environment and communications distance is found to be a free-insertion Lissajous orbit around the first co-linear Lagrange point of the Sun-Earth system L1, 1.5x 10^6 km from Earth. In order to transfer SMART-2/LISA Pathfinder from a low Earth orbit, where it will be placed by a small launcher, the spacecraft carries out a number of apogee-raise manoeuvres, which ultimatively place it to a parabolic escape trajectory towards L1. The challenges of the design of a small mission are met, fulfilling the very demanding technology demonstration requirements without creating excessive requirements on the launch system or the ground segment.Comment: 7 pages, 6 figures, 5th International LISA Symposium, see http://www.landisoft.de/Markus-Landgra

Outcome of renal grafts after simultaneous kidney/ pancreas transplantation

Nineteen patients with endstage renal failure due to Type 1 (insulin-dependent) diabetes mellitus received simultaneous pancreas/kidney transplants using bladder drainage technique. Another group of 25 Type 1 diabetic patients received pancreas/kidney transplants by the duct occlusion technique. We observed a higher incidence of rejection episodes in the patients of the bladder drainage group than those in the duct occlusion group, 14 of 19 patients (74%) vs 7 of 25 (28%) respectively. Anti CD3 antibodies (Orthoclone, OKT3) as a part of induction treatment was used more often in the bladder drainage group (58%) than in the control group (20%)

Prion-induced neurotoxicity: Possible role for cell cycle activity and DNA damage response.

Protein misfolding neurodegenerative diseases arise through neurotoxicity induced by aggregation of host proteins. These conditions include Alzheimer's disease, Huntington's disease, Parkinson's disease, motor neuron disease, tauopathies and prion diseases. Collectively, these conditions are a challenge to society because of the increasing aged population and through the real threat to human food security by animal prion diseases. It is therefore important to understand the cellular and molecular mechanisms that underlie protein misfolding-induced neurotoxicity as this will form the basis for designing strategies to alleviate their burden. Prion diseases are an important paradigm for neurodegenerative conditions in general since several of these maladies have now been shown to display prion-like phenomena. Increasingly, cell cycle activity and the DNA damage response are recognised as cellular events that participate in the neurotoxic process of various neurodegenerative diseases, and their associated animal models, which suggests they are truly involved in the pathogenic process and are not merely epiphenomena. Here we review the role of cell cycle activity and the DNA damage response in neurodegeneration associated with protein misfolding diseases, and suggest that these events contribute towards prion-induced neurotoxicity. In doing so, we highlight PrP transgenic Drosophila as a tractable model for the genetic analysis of transmissible mammalian prion disease.Supported by The NC3Rs No. NC/K000462/1 (in part).This is the final published version. It first appeared at http://dx.doi.org/10.5501/wjv.v4.i3.188

A Gas Monitoring Chamber for the ATLAS Muon Monitored Drift Tube(MDT) System

The ATLAS Muon Spectrometer incorporates MDT precision chambers used for precise track reconstruction. Since the MDT resolution depends crucially on the electron drift velocity in the operating gas, a monitoring chamber is designed and constructed to precisely monitor the gas properties in real time. This chamber continuously samples the operating gas and measures the electron drift velocity in the operating gas over a wide range of electric field strength with very high resolution and short response time. In order to validate the feasibility and optimize the design, extensive simulations based on Garfield and 3D/2D finite element method(FEM) are done, which include mechanics, electrostatics, thermodynamics and computational fluid dynamics(CFD). This monitoring chamber enables the measurement of the drift velocity spectra over a varying electric field with a wide range, then very small changes and contaminations of the gas mixture can be detected. Results obtained at CERN and in the lab will be presented as well

Comparing view-based and map-based semantic labelling in real-time SLAM

Generally capable Spatial AI systems must build persistent scene representations where geometric models are combined with meaningful semantic labels. The many approaches to labelling scenes can be divided into two clear groups: view-based which estimate labels from the input view-wise data and then incrementally fuse them into the scene model as it is built; and map-based which label the generated scene model. However, there has so far been no attempt to quantitatively compare view-based and map-based labelling. Here, we present an experimental framework and comparison which uses real-time height map fusion as an accessible platform for a fair comparison, opening up the route to further systematic research in this area