Modulation of kainic acid neurotoxicity in rats

1. Systemically administered kainic acid causes a dose dependent increase in the amount of peripheral benzodiazepine receptor in the rat hippocampus, as assessed by [3H]PK11195 binding. 2. This increase in binding is due to an increase in Bmax and not K0. The increase in PK11195 binding indicates that reactive gliosis has occurred and, by inference, neuronal loss. 3. The kainic acid induced elevation in binding is blocked by the non-NMDA antagonist GYKI 52466 and the NMDA antagonists MK801 and CPP. 4. The adenosine A1 receptor agonist R-phenylisopropyladenosine (R-PIA) is able to attenuate the kainic acid induced neuronal loss in a dose dependent and time dependent manner. 5. The R-PIA response is blocked by 8-cyclopentyl,-l ,3- dipropylxanthine (DPCPX) in a dose dependent manner, although DPCPX is unable to potentiate kainate induced neurotoxicity. 6. 8-p-sulfophenyltheophylline (8-SPT), is unable to cross the blood-brain barrier, and is unable to block the R-PIA induced neuroprotection indicating that the R-PIA effect is centrally mediated. 7. Kynurenine, but not kynurenic acid or tryptophan is able to attenuate kainic acid induced neurotoxicity in a dose dependent manner. 8. Kainic acid and potassium chloride (KCl) are able to release [3H] glutamate from hippocampal slices in a dose dependent manner. 9. The kainic acid induced elevation induces a period of heightened release after the first, but not second or third stimulations, and this is not seen after either KCl or kainic acid/KCl stimulations. 10. The adenosine A1 agonist 2-chloroadenosine (5muM) is unable to block the kainic acid induced release of [3H] glutamate. 11. DPCPX (5nM) is able to induce a significant decrease in KCl stimulated release of [3H] glutamate but not the kainic acid induced release. 12. In conclusion, kainic acid is causing neurotoxicity in a dose dependent manner that is mediated through both non-NMDA and NMD A receptors, and can be attenuated by R-PIA, and ascorbate

Plausible energy demand patterns in a growing global economy with climate policy

Reducing the energy demand has become a key mechanism for limiting climate change, but there are practical limitations associated with large energy savings in a growing global economy and, importantly, its lower-income parts. Using new data on energy and GDP, we show that adopting the same near-term low-energy growth trajectory in all regions in IPCC scenarios limiting global warming to 1.5 °C presents an unresolved policy challenge. We discuss this challenge of combining energy demand reductions with robust income growth for the 6.4 billion people in middle- and low-income countries in light of the reliance of economic development on industrialization. Our results highlight the importance of addressing limits to energy demand reduction in integrated assessment modelling when regional economic development is powered by industrialization and of instead exploring faster energy supply decarbonization. Insights from development economics and other disciplines could help generate plausible assumptions given the financial, investment and stability issues involved

Atypical chemokine receptor 4 shapes activated B cell fate

Activated B cells can initially differentiate into three functionally distinct fates-early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells-by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell-intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate

Sources of Long-Range Anthropogenic Noise in Southern California and Implications for Tectonic Tremor Detection

Peer reviewe

Microbes central to human reproduction

As studies uncover the breadth of microbes associated with human life, opportunities will emerge to manipulate and augment their functions in ways that improve health and longevity. From involvement in the complexities of reproduction and fetal/infant development, to delaying the onset of disease, and indeed countering many maladies, microbes offer hope for human well-being. Evidence is emerging to suggest that microbes may play a beneficial role in body sites traditionally viewed as being sterile. Although further evidence is required, we propose that much of medical dogma is about to change significantly through recognition and understanding of these hitherto unrecognized microbe–host interactions. A meeting of the International Scientific Association for Probiotics and Prebiotics held in Aberdeen, Scotland (June 2014), presented new views and challenged established concepts on the role of microbes in reproduction and health of the mother and infant. This article summarizes some of the main aspects of these discussions

Demonstrating the Use of Optical Fibres in Biomedical Sensing:A Collaborative Approach for Engagement and Education

This paper demonstrates how research at the intersection of physics, engineering, biology and medicine can be presented in an interactive and educational way to a non-scientific audience. Interdisciplinary research with a focus on prevalent diseases provides a relatable context that can be used to engage with the public. Respiratory diseases are significant contributors to avoidable morbidity and mortality and have a growing social and economic impact. With the aim of improving lung disease understanding, new techniques in fibre-based optical endomicroscopy have been recently developed. Here, we present a novel engagement activity that resembles a bench-to-bedside pathway. The activity comprises an inexpensive educational tool ($70) adapted from a clinical optical endomicroscopy system and tutorials that cover state-of-the-art research. The activity was co-created by high school science teachers and researchers in a collaborative way that can be implemented into any engagement development process

The K2-HERMES Survey: Age and Metallicity of the Thick Disc

Asteroseismology is a promising tool to study Galactic structure and evolution because it can probe the ages of stars. Earlier attempts comparing seismic data from the {\it Kepler} satellite with predictions from Galaxy models found that the models predicted more low-mass stars compared to the observed distribution of masses. It was unclear if the mismatch was due to inaccuracies in the Galactic models, or the unknown aspects of the selection function of the stars. Using new data from the K2 mission, which has a well-defined selection function, we find that an old metal-poor thick disc, as used in previous Galactic models, is incompatible with the asteroseismic information. We show that spectroscopic measurements of [Fe/H] and [$\alpha$/Fe] elemental abundances from the GALAH survey indicate a mean metallicity of $\log (Z/Z_{\odot})=-0.16$ for the thick disc. Here $Z$ is the effective solar-scaled metallicity, which is a function of [Fe/H] and [$\alpha$/Fe]. With the revised disc metallicities, for the first time, the theoretically predicted distribution of seismic masses show excellent agreement with the observed distribution of masses. This provides an indirect verification of the asteroseismic mass scaling relation is good to within five percent. Using an importance-sampling framework that takes the selection function into account, we fit a population synthesis model of the Galaxy to the observed seismic and spectroscopic data. Assuming the asteroseismic scaling relations are correct, we estimate the mean age of the thick disc to be about 10 Gyr, in agreement with the traditional idea of an old $\alpha$-enhanced thick disc.Comment: 21 pages, submitted to MNRA

A Simple and Practical Approach to Unit Testing: The JML and JUnit Way

Writing unit test code is labor-intensive, hence it is often not done as an integral part of programming. However, unit testing is a practical approach to increasing the correctness and quality of software; for example, the Extreme Programming approach relies on frequent unit testing. In this paper we present a new approach that makes writing unit tests easier. It uses a formal specification language\u27s runtime assertion checker to decide whether methods are working correctly, thus automating the writing of unit test oracles. These oracles can be easily combined with hand-written test data. Instead of writing testing code, the programmer writes formal specifications (e.g., pre- and postconditions). This makes the programmer\u27s task easier, because specifications are more concise and abstract than the equivalent test code, and hence more readable and maintainable. Furthermore, by using specifications in testing, specification errors are quickly discovered, so the specifications are more likely to provide useful documentation and inputs to other tools. We have implemented this idea using the Java Modeling Language (JML) and the JUnit testing framework, but the approach could be easily implemented with other combinations of formal specification languages and unit test tools

A Simple and Practical Approach to Unit Testing: The JML and JUnit Way

Writing unit test code is labor-intensive, hence it is often not done as an integral part of programming. However, unit testing is a practical approach to increasing the correctness and quality of software; for example, the Extreme Programming approach relies on frequent unit testing. In this paper we present a new approach that makes writing unit tests easier. It uses a formal specification language\u27s runtime assertion checker to decide whether methods are working correctly, thus automating the writing of unit test oracles. These oracles can be easily combined with hand-written test data. Instead of writing testing code, the programmer writes formal specifications (e.g., pre- and postconditions). This makes the programmer\u27s task easier, because specifications are more concise and abstract than the equivalent test code, and hence more readable and maintainable. Furthermore, by using specifications in testing, specification errors are quickly discovered, so the specifications are more likely to provide useful documentation and inputs to other tools. We have implemented this idea using the Java Modeling Language (JML) and the JUnit testing framework, but the approach could be easily implemented with other combinations of formal specification languages and unit test tools