Effects of D-amino acid oxidase inhibition on memory performance and long-term potentiation in vivo

N-methyl-d-aspartate receptor (NMDAR) activation can initiate changes in synaptic strength, evident as long-term potentiation (LTP), and is a key molecular correlate of memory formation. Inhibition of d-amino acid oxidase (DAAO) may increase NMDAR activity by regulating d-serine concentrations, but which neuronal and behavioral effects are influenced by DAAO inhibition remain elusive. In anesthetized rats, extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded before and after a theta frequency burst stimulation (TBS) of the Schaffer collateral pathway of the CA1 region in the hippocampus. Memory performance was assessed after training with tests of contextual fear conditioning (FC, mice) and novel object recognition (NOR, rats). Oral administration of 3, 10, and 30 mg/kg 4H-furo[3,2-b]pyrrole-5-carboxylic acid (SUN) produced dose-related and steady increases of cerebellum d-serine in rats and mice, indicative of lasting inhibition of central DAAO. SUN administered 2 h prior to training improved contextual fear conditioning in mice and novel object recognition memory in rats when tested 24 h after training. In anesthetized rats, LTP was established proportional to the number of TBS trains. d-cycloserine (DCS) was used to identify a submaximal level of LTP (5× TBS) that responded to NMDA receptor activation; SUN administered at 10 mg/kg 3–4 h prior to testing similarly increased in vivo LTP levels compared to vehicle control animals. Interestingly, in vivo administration of DCS also increased brain d-serine concentrations. These results indicate that DAAO inhibition increased NMDAR-related synaptic plasticity during phases of post training memory consolidation to improve memory performance in hippocampal-dependent behavioral tests

Mass extinctions and supernova explosions

A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be excluded and might even have been responsible for past extinction events.Comment: Chapter for forthcoming book: Handbook of Supernovae, P. Murdin and A. Alsabeti (eds.), Springer International Publishing (in press

The BBC, Austerity and Broadcasting the 1948 Olympic Games

Based on original archive research, including papers held in the BBC Written Archives Centre, and interviews with those involved, this paper analyses the historical importance for the BBC of the 1948 Games as the first publicly televised Olympics. In particular, the paper addresses the management of operations by the Head of Outside Broadcasting at the BBC, Seymour Joly de Lotbiniere. De Lotbiniere had been an important figure in the development of outside broadcasting commentaries during the inter-war period and was given the task of organising the radio and television coverage of the London Games in 1948. The paper examines the technical, operational and ideological issues raised by the event for the BBC and its legacy for the development of live televised outside broadcasts from sport. The analysis suggests the BBC’s ability to host international broadcasters became a matter of prestige and its forays into television a sign of its emerging post-War modernity

A new search for distant radio galaxies in the Southern hemisphere -- III. Optical spectroscopy and analysis of the MRCR--SUMSS sample

We have compiled a sample of 234 ultra-steep-spectrum(USS)-selected radio sources in order to find high-redshift radio galaxies (HzRGs). The sample is in the southern sky at -40 deg < DEC < -30 deg which is the overlap region of the 408-MHz Revised Molonglo Reference Catalogue, 843-MHz Sydney University Molonglo Sky Survey (the MRCR--SUMSS sample) and the 1400-MHz NRAO VLA Sky Survey. This is the third in a series of papers on the MRCR--SUMSS sample. Here we present optical spectra from the ANU 2.3-m telescope, ESO New Technology Telescope and ESO Very Large Telescope for 52 of the identifications from Bryant et al. (2009, Paper II), yielding redshifts for 36 galaxies, 13 of which have z>2. We analyse the K-z distribution and compare 4-arcsec-aperture magnitudes with 64-kpc aperture magnitudes in several surveys from the literature; the MRCR--SUMSS sample is found to be consistent with models for 10^{11}-10^{12} solar mass galaxies. Dispersions about the fits in the K-z plot support passive evolution of radio galaxy hosts since z>3. By comparing USS-selected samples in the literature, we find that the resultant median redshift of the samples shown is not dependent on the flux density distribution or selection frequency of each sample. In addition, our finding that the majority of the radio spectral energy distributions remain straight over a wide frequency range suggests that a k-correction is not responsible for the success of USS-selection in identifying high redshift radio galaxies and therefore the steep radio spectra may be intrinsic to the source or a product of the environment. Two galaxies have been found to have both compact radio structures and strong self-absorption in the Ly-alpha line, suggesting they are surrounded by a dense medium...abridged.Comment: Accepted for MNRAS. 25 page

The Max-Planck-Institute global ocean/sea ice model with orthogonal curvilinear coordinates

The Hamburg Ocean Primitive Equation model has undergone significant development in recent years. Most notable is the treatment of horizontal discretisation which has undergone transition from a staggered E-grid to an orthogonal curvilinear C-grid. The treatment of subgridscale mixing has been improved by the inclusion of a new formulation of bottom boundary layer (BBL) slope convection, an isopycnal diffusion scheme, and a Gent and McWilliams style eddy-induced mixing parameterisation. The model setup described here has a north pole over Greenland and a south pole on the coast of the Weddell Sea. This gives relatively high resolution in the sinking regions associated with the thermohaline circulation. Results are presented from a 450 year climatologically forced integration. The forcing is a product of the German Ocean Model Intercomparison Project and is derived from the European Centre for Medium Range Weather Forecasting reanalysis. The main emphasis is on the model's representation of key quantities that are easily associated with the ocean's role in the global climate system. The global and Atlantic northward poleward heat transports have peaks of 1.43 and 0.84 PW, at 18degrees and 21degrees N respectively. The Atlantic meridional overturning streamfunction has a peak of 15.7 Sv in the North Atlantic and an outflow of 11.9 Sv at 30degrees S. Comparison with a simulation excluding BBL shows that the scheme is responsible for up to a 25% increase in North Atlantic heat transport, with significant improvement of the depths of convection in the Greenland, Labrador and Irminger Seas. Despite the improvements, comparison with observations shows the heat transport still to be too weak. Other outstanding problems include an incorrect Gulf Stream pathway, a too strong Antarctic Circumpolar Current, and a too weak renewal of Antarctic Intermediate Water. Nevertheless, the model has been coupled to the atmospheric GCM ECHAM5 and run successfully for over 250 years without any surface flux corrections. (C) 2002 Elsevier Science Ltd. All rights reserved

Temporal regularity of the environment drives time perception

It’s reasonable to assume that a regularly paced sequence should be perceived as regular, but here we show that perceived regularity depends on the context in which the sequence is embedded. We presented one group of participants with perceptually regularly paced sequences, and another group of participants with mostly irregularly paced sequences (75% irregular, 25% regular). The timing of the final stimulus in each sequence could be varied. In one experiment, we asked whether the last stimulus was regular or not. We found that participants exposed to an irregular environment frequently reported perfectly regularly paced stimuli to be irregular. In a second experiment, we asked participants to judge whether the final stimulus was presented before or after a flash. In this way, we were able to determine distortions in temporal perception as changes in the timing necessary for the sound and the flash to be perceived synchronous. We found that within a regular context, the perceived timing of deviant last stimuli changed so that the relative anisochrony appeared to be perceptually decreased. In the irregular context, the perceived timing of irregular stimuli following a regular sequence was not affected. These observations suggest that humans use temporal expectations to evaluate the regularity of sequences and that expectations are combined with sensory stimuli to adapt perceived timing to follow the statistics of the environment. Expectations can be seen as a-priori probabilities on which perceived timing of stimuli depend

Violent aggression predicted by multiple pre-adult environmental hits

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention

Phylogeny Disambiguates the Evolution of Heat-Shock cis-Regulatory Elements in Drosophila

Heat-shock genes have a well-studied control mechanism for their expression that is mediated through cis-regulatory motifs known as heat-shock elements (HSEs). The evolution of important features of this control mechanism has not been investigated in detail, however. Here we exploit the genome sequencing of multiple Drosophila species, combined with a wealth of available information on the structure and function of HSEs in D. melanogaster, to undertake this investigation. We find that in single-copy heat shock genes, entire HSEs have evolved or disappeared 14 times, and the phylogenetic approach bounds the timing and direction of these evolutionary events in relation to speciation. In contrast, in the multi-copy gene Hsp70, the number of HSEs is nearly constant across species. HSEs evolve in size, position, and sequence within heat-shock promoters. In turn, functional significance of certain features is implicated by preservation despite this evolutionary change; these features include tail-to-tail arrangements of HSEs, gapped HSEs, and the presence or absence of entire HSEs. The variation among Drosophila species indicates that the cis-regulatory encoding of responsiveness to heat and other stresses is diverse. The broad dimensions of variation uncovered are particularly important as they suggest a substantial challenge for functional studies

Towards a framework for attention cueing in instructional animations: Guidelines for research and design

This paper examines the transferability of successful cueing approaches from text and static visualization research to animations. Theories of visual attention and learning as well as empirical evidence for the instructional effectiveness of attention cueing are reviewed and, based on Mayer’s theory of multimedia learning, a framework was developed for classifying three functions for cueing: (1) selection—cues guide attention to specific locations, (2) organization—cues emphasize structure, and (3) integration—cues explicate relations between and within elements. The framework was used to structure the discussion of studies on cueing in animations. It is concluded that attentional cues may facilitate the selection of information in animations and sometimes improve learning, whereas organizational and relational cueing requires more consideration on how to enhance understanding. Consequently, it is suggested to develop cues that work in animations rather than borrowing effective cues from static representations. Guidelines for future research on attention cueing in animations are presented