Rapidly progressive post-transplant lymphoproliferative disease following withdrawal of sirolimus

Sirolimus, a potent inhibitor of B- and T-cell activation, is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder following the withdrawal of sirolimus

A pre-Caloris synchronous rotation for Mercury

The planet Mercury is locked in a spin-orbit resonance where it rotates three times about its spin axis for every two orbits about the Sun. The current explanation for this unique state assumes that the initial rotation of this planet was prograde and rapid, and that tidal torques decelerated the planetary spin to this resonance. When core-mantle boundary friction is accounted for, capture into the 3/2 resonance occurs with a 26% probability, but the most probable outcome is capture into one of the higher-order resonances. Here we show that if the initial rotation of Mercury were retrograde, this planet would be captured into synchronous rotation with a 68% probability. Strong spatial variations of the impact cratering rate would have existed at this time, and these are shown to be consistent with the distribution of pre-Calorian impact basins observed by Mariner 10 and MESSENGER. Escape from this highly stable resonance is made possible by the momentum imparted by large basin-forming impact events, and capture into the 3/2 resonance occurs subsequently under favourable conditions.Comment: Nature Geosci., 201

Bayesian time series analysis of terrestrial impact cratering

Giant impacts by comets and asteroids have probably had an important influence on terrestrial biological evolution. We know of around 180 high velocity impact craters on the Earth with ages up to 2400Myr and diameters up to 300km. Some studies have identified a periodicity in their age distribution, with periods ranging from 13 to 50Myr. It has further been claimed that such periods may be causally linked to a periodic motion of the solar system through the Galactic plane. However, many of these studies suffer from methodological problems, for example misinterpretation of p-values, overestimation of significance in the periodogram or a failure to consider plausible alternative models. Here I develop a Bayesian method for this problem in which impacts are treated as a stochastic phenomenon. Models for the time variation of the impact probability are defined and the evidence for them in the geological record is compared using Bayes factors. This probabilistic approach obviates the need for ad hoc statistics, and also makes explicit use of the age uncertainties. I find strong evidence for a monotonic decrease in the recorded impact rate going back in time over the past 250Myr for craters larger than 5km. The same is found for the past 150Myr when craters with upper age limits are included. This is consistent with a crater preservation/discovery bias modulating an otherwise constant impact rate. The set of craters larger than 35km (so less affected by erosion and infilling) and younger than 400Myr are best explained by a constant impact probability model. A periodic variation in the cratering rate is strongly disfavoured in all data sets. There is also no evidence for a periodicity superimposed on a constant rate or trend, although this more complex signal would be harder to distinguish.Comment: Minor typos corrected in arXiv v2. Erratum (minor notation corrections) corrected in arXiv v3. (Erratum available from http://www.mpia-hd.mpg.de/~calj/craterTS_erratum.pdf

Sheep Updates 2005 - Part 7

This session covers eight papers from different authors: POSTERS 1. Sulpher in wool and its implications for fleece weight and sheep health, SM Liu, AC Schlink, JR Williams, CSIRO Livestock Industries Wembley WA, ME Dowling,JCGreef, Department of Agriculture Western Australia. 2. Stubbles for sheep: a reality check, Roy Butler, Keith Croker, Department of Agriculture Western Australia. 3. Genetic benchmarking using artificial insemination, LC Butler, JC Greeff, Department of Agriculture Western Australia. 4. The potential lambing performances of ewes in mixed age flocks, Kieth Croker, Department of Agriculture Western Australia, Rob Davidson, WAMMCO International, formally University of Western Australia, Ken Hart, Department of Agriculture Western Australia,Doug Harrington Cowcher Farms Narrogin, Mario D\u27Antuono, Department of Agriculture Western Australia. 5. National Livestock Identification System (Sheep) in Western Australia, Julian Gardner, Department of Agriculture Western Australia. DISPLAYS - TOOLS 6. To Feed or Not to Feed - I Only Hamlet had the Calculator!, Geoff Duddy, Livestock Officer(Sheep & Wool) Yanco. 7. WormBoss - a national Australian computer-based sheep worm control tool, RG Woodgate, Department of Agriculture Western Australia, A LeFeuvre, Queensland Department of Primary Industries and Fisheries, and Genie Pty Ltd, Warwick Qld, A Bailey, Department of Primary Industries, Water and Environment, Kings Meadow Tas, RB Besier, Department of Agriculture Western Australia, N. Campbell, Department of Primary Industries Victoria, Attwood Vic, I Carmichael, South Australian Research and Development Institute, Glenside SA, S. Love, NSW Department of Primary Industries, Armidale NSW. 8. \u27Eye in the sky\u27 takes guesswork out of farmers pasture decisions, Richard Stovold, Department of Land Informatio

The P2 Receptor Antagonist PPADS Supports Recovery from Experimental Stroke In Vivo

BACKGROUND: After ischemia of the CNS, extracellular adenosine 5'-triphosphate (ATP) can reach high concentrations due to cell damage and subsequent increase of membrane permeability. ATP may cause cellular degeneration and death, mediated by P2X and P2Y receptors. METHODOLOGY/PRINCIPAL FINDINGS: The effects of inhibition of P2 receptors by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on electrophysiological, functional and morphological alterations in an ischemia model with permanent middle cerebral artery occlusion (MCAO) were investigated up to day 28. Spontaneously hypertensive rats received PPADS or vehicle intracerebroventricularly 15 minutes prior MCAO for up to 7 days. The functional recovery monitored by qEEG was improved by PPADS indicated by an accelerated recovery of ischemia-induced qEEG changes in the delta and alpha frequency bands along with a faster and sustained recovery of motor impairments. Whereas the functional improvements by PPADS were persistent at day 28, the infarct volume measured by magnetic resonance imaging and the amount of TUNEL-positive cells were significantly reduced by PPADS only until day 7. Further, by immunohistochemistry and confocal laser scanning microscopy, we identified both neurons and astrocytes as TUNEL-positive after MCAO. CONCLUSION: The persistent beneficial effect of PPADS on the functional parameters without differences in the late (day 28) infarct size and apoptosis suggests that the early inhibition of P2 receptors might be favourable for the maintenance or early reconstruction of neuronal connectivity in the periinfarct area after ischemic incidents

Exploring the role of the Sun’s motion in terrestrial comet impacts

The cratering record on the Earth and Moon shows that our planet has been exposed to high velocity impacts for much or all of its existence. Some of these craters were produced by the impact of long-period comets (LPCs). These probably originated in the Oort Cloud, and were put into their present orbits through gravitational perturbations arising from the Galactic tide and stellar encounters, both of which are modulated by the solar motion about the Galaxy. Here we construct dynamical models of these mechanisms in order to predict the time-varying impact rate of LPCs and the angular distribution of their perihelia (which is observed to be non-uniform). Comparing the predictions of these dynamical models with other models, we conclude that cometary impacts induced by the solar motion contribute only a small fraction of terrestrial impact craters over the past 250 Myr. Over this time-scale, the apparent cratering rate is dominated by a secular increase towards the present, which might be the result of the disruption of a large asteroid. Our dynamical models, together with the solar apex motion, predict a non-uniform angular distribution of the perihelia, without needing to invoke the existence of a massive body in the outer Oort Cloud. Our results are reasonably robust to changes in the parameters of the Galaxy model, Oort Cloud, and stellar encounters.Peer reviewedFinal Accepted Versio

Recent evolutions of gender, state feminism and care models in Latin America and Europe

Production of INCASI Project H2020-MSCA-RISE-2015 GA 691004This chapter presents and characterises the way in which, in the twenty-first century, after years of feminist struggles inside and outside of institutions, gender relations are organised in the different countries of the INCASI project (on the European side, Spain, Italy, Finland, France and the United Kingdom, on the side of the South American Southern Cone, Argentina, Brazil, Chile and Uruguay). It pays special attention to the implementation of feminist issues on political agendas, and in particular the assignment of women to unpaid care work-an aspect of the power continuum that we look to relate to other aspects. Gradually and for almost a century all countries in both continents have granted women the status of subjects, citizens and employees. However, the conditions, challenges and timelines of this process differ considerably from one continent to another, so they need to be addressed separately. The neoliberal era did not have the same impact in Europe as it did in South America (nor was it exactly the same between particular European countries or among South American ones)

Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

Depression of glutamate and GABA release by presynaptic GABAB receptors in the entorhinal cortex in normal and chronically epileptic rats

Presynaptic GABAB receptors (GABABR) control glutamate and GABA release at many synapses in the nervous system. In the present study we used whole-cell patch-clamp recordings of spontaneous excitatory and inhibitory synaptic currents in the presence of TTX to monitor glutamate and GABA release from synapses in layer II and V of the rat entorhinal cortex (EC)in vitro. In both layers the release of both transmitters was reduced by application of GABABR agonists. Quantitatively, the depression of GABA release in layer II and layer V, and of glutamate release in layer V was similar, but glutamate release in layer II was depressed to a greater extent. The data suggest that the same GABABR may be present on both GABA and glutamate terminals in the EC, but that the heteroreceptor may show a greater level of expression in layer II. Studies with GABABR antagonists suggested that neither the auto- nor the heteroreceptor was consistently tonically activated by ambient GABA in the presence of TTX. Studies in EC slices from rats made chronically epileptic using a pilocarpine model of temporal lobe epilepsy revealed a reduced effectiveness of both auto- and heteroreceptor function in both layers. This could suggest that enhanced glutamate and GABA release in the EC may be associated with the development of the epileptic condition. Copyright © 2006 S. Karger AG

Systematic review and meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke: an update

Interleukin-1 receptor antagonist (IL-1 RA) is an anti-inflammatory protein used clinically to treat rheumatoid arthritis and is considered a promising candidate therapy for stroke. Here, we sought to update the existing systematic review and meta-analysis of IL-1 RA in models of ischaemic stroke, published in 2009, to assess efficacy, the range of circumstances in which efficacy has been tested and whether the data appear to be confounded due to reported study quality and publication bias. We included 25 sources of data, 11 of which were additional to the original review. Overall, IL-1 RA reduced infarct volume by 36.2 % (95 % confidence interval 31.6–40.7, n = 76 comparisons from 1283 animals). Assessments for publication bias suggest 30 theoretically missing studies which reduce efficacy to 21.9 % (17.3–26.4). Efficacy was higher where IL-1 RA was administered directly into the ventricles rather than peripherally, and studies not reporting allocation concealment during the induction of ischaemia reported larger treatment effects. The preclinical data supporting IL-1 RA as a candidate therapy for ischaemic stroke have improved. The reporting of measures to reduce the risk of bias has improved substantially in this update, and studies now include the use of animals with relevant co-morbidities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12975-016-0489-z) contains supplementary material, which is available to authorized users