Excitatory amino acids and intracellular pH in motoneurons of the isolated frog spinal cord

Double-barrelled pH-sensitive micro-electrodes were used to measure changes of intracellular and extracellular pH in and around motoneurons of the isolated frog spinal cord during application of excitatory amino acids. It was found that N-methyl- -aspartate, quisqualate and kainate produced a concentration-dependent intracellular acidification. Extracellularly, triphasic pH changes (acid-alkaline-acid going pH transients) were observed during the action of these amino acids. The possible significance of such pH changes for the physiological and pathophysiological effects of excitatory amino acids are discussed

The Laboratory-Based Intermountain Validated Exacerbation (LIVE) Score Identifies Chronic Obstructive Pulmonary Disease Patients at High Mortality Risk.

Background: Identifying COPD patients at high risk for mortality or healthcare utilization remains a challenge. A robust system for identifying high-risk COPD patients using Electronic Health Record (EHR) data would empower targeting interventions aimed at ensuring guideline compliance and multimorbidity management. The purpose of this study was to empirically derive, validate, and characterize subgroups of COPD patients based on routinely collected clinical data widely available within the EHR. Methods: Cluster analysis was used in 5,006 patients with COPD at Intermountain to identify clusters based on a large collection of clinical variables. Recursive Partitioning (RP) was then used to determine a preferred tree that assigned patients to clusters based on a parsimonious variable subset. The mortality, COPD exacerbations, and comorbidity profile of the identified groups were examined. The findings were validated in an independent Intermountain cohort and in external cohorts from the United States Veterans Affairs (VA) and University of Chicago Medicine systems. Measurements and Main Results: The RP algorithm identified five LIVE Scores based on laboratory values: albumin, creatinine, chloride, potassium, and hemoglobin. The groups were characterized by increasing risk of mortality. The lowest risk, LIVE Score 5 had 8% 4-year mortality vs. 56% in the highest risk LIVE Score 1 (p < 0.001). These findings were validated in the VA cohort (n = 83,134), an expanded Intermountain cohort (n = 48,871) and in the University of Chicago system (n = 3,236). Higher mortality groups also had higher COPD exacerbation rates and comorbidity rates. Conclusions: In large clinical datasets across different organizations, the LIVE Score utilizes existing laboratory data for COPD patients, and may be used to stratify risk for mortality and COPD exacerbations

Ca2+ elevations disrupt interactions between intraflagellar transport and the flagella membrane in Chlamydomonas

The movement of ciliary membrane proteins is directed by transient interactions with intraflagellar transport (IFT) trains. The green alga Chlamydomonas has adapted this process for gliding motility, using retrograde IFT motors to move adhesive glycoproteins in the flagella membrane. Ca2+ signalling contributes directly to the gliding process, although uncertainty remains over the mechanism through which it acts. Here, we show that flagella Ca2+ elevations initiate the movement of paused retrograde IFT trains, which accumulate at the distal end of adherent flagella, but do not influence other IFT processes. On highly adherent surfaces, flagella exhibit high frequency Ca2+ elevations that prevent the accumulation of paused retrograde IFT trains. Flagella Ca2+ elevations disrupt the IFT dependent movement of microspheres along the flagella membrane, suggesting that Ca2+ acts by directly disrupting an interaction between retrograde IFT trains and flagella membrane glycoproteins. By regulating the extent to which glycoproteins on the flagella surface interact with IFT motor proteins on the axoneme, this signalling mechanism allows precise control of traction force and gliding motility in adherent flagella

The vulnerability of public spaces: challenges for UK hospitals under the 'new' terrorist threat

This article considers the challenges for hospitals in the United Kingdom that arise from the threats of mass-casualty terrorism. Whilst much has been written about the role of health care as a rescuer in terrorist attacks and other mass-casualty crises, little has been written about health care as a victim within a mass-emergency setting. Yet, health care is a key component of any nation's contingency planning and an erosion of its capabilities would have a significant impact on the generation of a wider crisis following a mass-casualty event. This article seeks to highlight the nature of the challenges facing elements of UK health care, with a focus on hospitals both as essential contingency responders under the United Kingdom's civil contingencies legislation and as potential victims of terrorism. It seeks to explore the potential gaps that exist between the task demands facing hospitals and the vulnerabilities that exist within them

Climate geoengineering: issues of path-dependence and socio-technical lock-in

As academic and policy interest in climate geoengineering grows, the potential irreversibility of technological developments in this domain has been raised as a pressing concern. The literature on socio-technical lock-in and path dependence is illuminating in helping to situate current concerns about climate geoengineering and irreversibility in the context of academic understandings of historical socio-technical development and persistence. This literature provides a wealth of material illustrating the pervasiveness of positive feedbacks of various types (from the discursive to the material) leading to complex socio-technical entanglements which may resist change and become inflexible even in the light of evidence of negative impacts. With regard to climate geoengineering, there are concerns that geoengineering technologies might contribute so-called ‘carbon lock-in’, or become irreversibly ‘locked-in’ themselves. In particular, the scale of infrastructures that geoengineering interventions would require, and the issue of the so-called ‘termination effect’ have been discussed in these terms. Despite the emergent and somewhat ill-defined nature of the field, some authors also suggest that the extant framings of geoengineering in academic and policy literatures may already demonstrate features recognizable as forms of cognitive lock-in, likely to have profound implications for future developments in this area. While the concepts of path-dependence and lock-in are the subject of ongoing academic critique, by drawing analytical attention to these pervasive processes of positive feedback and entanglement, this literature is highly relevant to current debates around geoengineering

Differential ability of the dorsal and ventral rat hippocampus to exhibit group I metabotropic glutamate receptor-dependent synaptic and intrinsic plasticity.

BACKGROUND: The hippocampus is critically involved in learning and memory processes. Although once considered a relatively homogenous structure, it is now clear that the hippocampus can be divided along its longitudinal axis into functionally distinct domains, responsible for the encoding of different types of memory or behaviour. Although differences in extrinsic connectivity are likely to contribute to this functional differentiation, emerging evidence now suggests that cellular and molecular differences at the level of local hippocampal circuits may also play a role. METHODS: In this study, we have used extracellular field potential recordings to compare basal input/output function and group I metabotropic glutamate receptor-dependent forms of synaptic and intrinsic plasticity in area CA1 of slices taken from the dorsal and ventral sectors of the adult rat hippocampus. RESULTS: Using two extracellular electrodes to simultaneously record field EPSPs and population spikes, we show that dorsal and ventral hippocampal slices differ in their basal levels of excitatory synaptic transmission, paired-pulse facilitation, and EPSP-to-Spike coupling. Furthermore, we show that slices taken from the ventral hippocampus have a greater ability than their dorsal counterparts to exhibit long-term depression of synaptic transmission and EPSP-to-Spike potentiation induced by transient application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine. CONCLUSIONS: Together, our results provide further evidence that the information processing properties of local hippocampal circuits differ in the dorsal and ventral hippocampal sectors, and that these differences may in turn contribute to the functional differentiation that exists along the hippocampal longitudinal axis.Medical Research Council (grant numbers: G0601813; MR/K023098/1)

Risks, alternative knowledge strategies and democratic legitimacy: the conflict over co-incineration of hazardous industrial waste in Portugal.

The decision to incinerate hazardous industrial waste in cement plants (the socalled ‘co-incineration’ process) gave rise to one of the most heated environmental conflicts ever to take place in Portugal. The bitterest period was between 1997 and 2002, after the government had made a decision. Strong protests by residents, environmental organizations, opposition parties, and some members of the scientific community forced the government to backtrack and to seek scientific legitimacy for the process through scientific expertise. The experts ratified the government’s decision, stating that the risks involved were socially acceptable. The conflict persisted over a decade and ended up clearing the way for a more sustainable method over which there was broad social consensus – a multifunctional method which makes it possible to treat, recover and regenerate most wastes. Focusing the analysis on this conflict, this paper has three aims: (1) to discuss the implications of the fact that expertise was ‘confiscated’ after the government had committed itself to the decision to implement co-incineration and by way of a reaction to the atmosphere of tension and protest; (2) to analyse the uses of the notions of ‘risk’ and ‘uncertainty’ in scientific reports from both experts and counter-experts’ committees, and their different assumptions about controllability and criteria for considering certain practices to be sufficiently safe for the public; and (3) to show how the existence of different technical scientific and political attitudes (one more closely tied to government and the corporate interests of the cement plants, the other closer to the environmental values of reuse and recycling and respect for the risk perception of residents who challenged the facilities) is closely bound up with problems of democratic legitimacy. This conflict showed how adopting more sustainable and lower-risk policies implies a broader view of democratic legitimacy, one which involves both civic movements and citizens themselves

The ethics of uncertainty for data subjects

Modern health data practices come with many practical uncertainties. In this paper, I argue that data subjects’ trust in the institutions and organizations that control their data, and their ability to know their own moral obligations in relation to their data, are undermined by significant uncertainties regarding the what, how, and who of mass data collection and analysis. I conclude by considering how proposals for managing situations of high uncertainty might be applied to this problem. These emphasize increasing organizational flexibility, knowledge, and capacity, and reducing hazard

Rapid and Differential Regulation of AMPA and Kainate Receptors at Hippocampal Mossy Fibre Synapses by PICK1 and GRIP

AbstractWe identified four PDZ domain-containing proteins, syntenin, PICK1, GRIP, and PSD95, as interactors with the kainate receptor (KAR) subunits GluR52b, GluR52c, and GluR6. Of these, we show that both GRIP and PICK1 interactions are required to maintain KAR-mediated synaptic function at mossy fiber-CA3 synapses. In addition, PKCα can phosphorylate ct-GluR52b at residues S880 and S886, and PKC activity is required to maintain KAR-mediated synaptic responses. We propose that PICK1 targets PKCα to phosphorylate KARs, causing their stabilization at the synapse by an interaction with GRIP. Importantly, this mechanism is not involved in the constitutive recycling of AMPA receptors since blockade of PDZ interactions can simultaneously increase AMPAR- and decrease KAR-mediated synaptic transmission at the same population of synapses