Differentiating the effects of negative state on optimism and the implicit perception of everyday injury risk

To date no research has examined the effects of negative state on the perception of everyday injury risk. Instead, studies have focussed more broadly on the relationship between mood and self- reported optimism. The present study had two aims. Firstly, to assess the effect of incidental anxiety on implicit injury risk perception using a modified Implicit Association Test (IAT). Secondly, it sought to compare any effect with that on a conventional measure of risk perception (optimism). In line with previous research, anxious participants perceived more risk (were less optimistic). In contrast, there was no significant correlation between anxiety and the implicit perception of everyday injury risk. Theoretical and practical implications are discussed

Tonic and phasic nitric oxide signals in hippocampal long-term potentiation

Nitric oxide ( NO) participates in long-term potentiation (LTP) and other forms of synaptic plasticity in many different brain areas but where it comes from and how it acts remain controversial. Using rat and mouse hippocampal slices, we tested the hypothesis that tonic and phasic NO signals are needed and that they derive from different NO synthase isoforms. NMDA increased NO production in a manner that was potently inhibited by three different neuronal NO synthase ( nNOS) inhibitors. Tonic NO could be monitored after sensitizing guanylyl cyclase-coupled NO receptors, allowing the very low ambient NO concentrations to be detected by cGMP measurement. The levels were unaffected by inhibition of NMDA receptors, nNOS, or the inducible NO synthase ( iNOS). iNOS was also undetectable in protein or activity assays. Tonic NO was susceptible to agents inhibiting endothelial NO synthase ( eNOS) and was missing in eNOS knock-out mice. The eNOS knock-out sexhibited a deficiency in LTP resembling that seen in wild-types treated with a NO synthase inhibitor. LTP in the knock-outs could be fully restored by supplying a low level of NO exogenously. Inhibition of nNOS also caused a major loss of LTP, particularly of late-LTP. Again, exogenous NO could compensate, but higher concentrations were needed compared with those restoring LTP in the eNOS knock-outs. It is concluded that tonic and phasic NO signals are both required for hippocampal LTP and the two are generated, respectively, by eNOS and nNOS, the former in blood vessels and the latter in neurons

Cytochrome P450 oxidoreductase participates in nitric oxide consumption by rat brain

In low nanomolar concentrations, NO (nitric oxide) functions as a transmitter in brain and other tissues, whereas near-micromolar NO concentrations are associated with toxicity and cell death. Control of the NO concentration, therefore, is critical for proper brain function, but, although its synthesis pathway is well-characterized, the major route of breakdown of NO in brain is unclear. Previous observations indicate that brain cells actively consume NO at a high rate. The mechanism of this consumption was pursued in the present study. NO consumption by a preparation of central glial cells was abolished by cell lysis and recovered by addition of NADPH. NADPH-dependent consumption of NO localized to cell membranes and was inhibited by proteinase K, indicating the involvement of a membrane-bound protein. Purification of this activity yielded CYPOR (cytochrome P450 oxidoreductase). Antibodies against CYPOR inhibited NO consumption by brain membranes and the amount of CYPOR in several cell types correlated with their rate of NO consumption. NO was also consumed by purified CYPOR but this activity was found to depend on the presence of the vitamin E analogue Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid), included in the buffer as a precaution against inadvertent NO consumption by lipid peroxidation. In contrast, NO consumption by brain membranes was independent of Trolox. Hence, it appears that, during the purification process, CYPOR becomes separated from a partner needed for NO consumption. Cytochrome P450 inhibitors inhibited NO consumption by brain membranes, making these proteins likely candidates

Signaling from blood vessels to CNS axons through nitric oxide

Brain function is usually perceived as being performed by neurons with the support of glial cells, the network of blood vessels situated nearby serving simply to provide nutrient and to dispose of metabolic waste. Revising this view, we find from experiments on a rodent central white matter tract (the optic nerve) in vitro that microvascular endothelial cells signal persistently to axons using nitric oxide (NO) derived from the endothelial NO synthase (eNOS). The endogenous NO acts to stimulate guanylyl cyclase-coupled NO receptors in the axons, leading to a raised cGMP level which then causes membrane depolarization, apparently by directly engaging hyperpolarization-activated cyclic nucleotide-gated ion channels. The tonic depolarization and associated endogenous NO-dependent cGMP generation was absent in optic nerves from mice lacking eNOS, although such nerves responded to exogenous NO, with raised cGMP generation in the axons and associated depolarization. In addition to the tonic activity, exposure of optic nerves to bradykinin, a classical stimulator of eNOS in endothelial cells, elicited reversible NO- and cGMP-dependent depolarization through activation of bradykinin B-2 receptors, to which eNOS is physically complexed. No contribution of other NO synthase isoforms to either the action of bradykinin or the continuous ambient NO level could be detected. The results suggest that microvascular endothelial cells participate in signal processing in the brain and can do so by generating both tonic and phasic NO signals

From synaptically localized to volume transmission by nitric oxide.

Nitric oxide (NO) functions widely as a transmitter/diffusible second messenger in the central nervous system, exerting physiological effects in target cells by binding to specialized guanylyl cyclase-coupled receptors, resulting in cGMP generation. Despite having many context-dependent physiological roles and being implicated in numerous disease states, there has been a lack of clarity about the ways that NO operates at the cellular and subcellular levels. Recently, several approaches have been used to try to gain a more concrete, quantitative understanding of this unique signalling pathway. These approaches have included analysing the kinetics of NO receptor function, real-time imaging of cellular NO signal transduction in target cells, and the use of ultrasensitive detector cells to record NO as it is being generated from native sources in brain tissue. The current picture is that, when formed in a synapse, NO is likely to act only very locally, probably mostly within the confines of that synapse, and to exist only in picomolar concentrations. Nevertheless, closely neighbouring synapses may also be within reach, raising the possibility of synaptic crosstalk. By engaging its enzyme-coupled receptors, the low NO concentrations are able to stimulate physiological (submicromolar) increases in cGMP concentration in an activity-dependent manner. When many NO-emitting neurones or synapses are active simultaneously in a tissue region, NO can act more like a volume transmitter to influence, and perhaps coordinate, the behaviour of cells within that region, irrespective of their identity and anatomical connectivity

Nitric Oxide Is Required for L-Type Ca(2+) Channel-Dependent Long-Term Potentiation in the Hippocampus.

Nitric oxide (NO) has long been implicated in the generation of long-term potentiation (LTP) and other types of synaptic plasticity, a role for which the intimate coupling between NMDA receptors (NMDARs) and the neuronal isoform of NO synthase (nNOS) is likely to be instrumental in many instances. While several types of synaptic plasticity depend on NMDARs, others do not, an example of which is LTP triggered by opening of L-type voltage-gated Ca(2+) channels (L-VGCCs) in postsynaptic neurons. In CA3-CA1 synapses in the hippocampus, NMDAR-dependent LTP (LTPNMDAR) appears to be primarily expressed postsynaptically whereas L-VGCC-dependent LTP (LTPL-VGCC), which often coexists with LTPNMDAR, appears mainly to reflect enhanced presynaptic transmitter release. Since NO is an excellent candidate as a retrograde messenger mediating post-to-presynaptic signaling, we sought to determine if NO functions in LTPL-VGCC in mouse CA3-CA1 synapses. When elicited by a burst type of stimulation with NMDARs and the associated NO release blocked, LTPL-VGCC was curtailed by inhibition of NO synthase or of the NO-receptor guanylyl cyclase to the same extent as occurred with inhibition of L-VGCCs. Unlike LTPNMDAR at these synapses, LTPL-VGCC was unaffected in mice lacking endothelial NO synthase, implying that the major source of the NO is neuronal. Transient delivery of exogenous NO paired with tetanic synaptic stimulation under conditions of NMDAR blockade resulted in a long-lasting potentiation that was sensitive to inhibition of NO-receptor guanylyl cyclase but was unaffected by inhibition of L-VGCCs. The results indicate that NO, acting through its second messenger cGMP, plays an unexpectedly important role in L-VGCC-dependent, NMDAR-independent LTP, possibly as a retrograde messenger generated in response to opening of postsynaptic L-VGCCs and/or as a signal acting postsynaptically, perhaps to facilitate changes in gene expression

After Atos Healthcare: is the Employment and Support Allowance fit for purpose and does the Work Capability Assessment have a future?

In June 2014 the BBC reported that it had seen a number of UK Department for Work and Pensions documents relating to the Employment and Support Allowance (ESA). These documents, which included six memos written by civil servants and government advisers, tell us very little that we did not know already; namely that the ESA is in crisis, and that waiting lists for assessment and appeals are unacceptable. However, what is significant is that these concerns are being raised within the Department for Work and Pensions itself. The underlying drift is that the question of whether the current model of ESA and Work Capability Assessment is sustainable is now firmly on the UK government’s radar

Building Community: A Tool Kit for Youth and Adults in Charting Assets and Creating Change

Extension workers around the country are discovering a new way to help communities become more of what they want to be, and link them to extension resources, through the use of Building Community: A Tool Kit for Youth and Adults In Charting Assets and Creating Change. Developed by the Innovation Center for Community and Youth Development with Extension partners, the tool kit focuses on the gifts that a community brings to their desire for change--gifts of the past, place, people, and relationships--and has proven itself to be a powerful tool for sustainable community development

Desperately seeking reductions in health inequalities: perspectives of UK researchers on past, present and future directions in health inequalities research

Following government commitments to reducing health inequalities from 1997 onwards, the UK has been recognised as a global leader in health inequalities research and policy. Yet health inequalities have continued to widen by most measures, prompting calls for new research agendas and advocacy to facilitate greater public support for the upstream policies that evidence suggests are required. However, there is currently no agreement as to what new research might involve or precisely what public health egalitarians ought to be advocating. This article presents an analysis of discussions among 52 researchers to consider the feasibility that research-informed advocacy around particular solutions to health inequalities may emerge in the UK. The data indicate there is a consensus that more should be been done to learn from post-1997 efforts to reduce health inequalities, and an obvious desire to provide clearer policy guidance in future. However, discussions as to where researchers should now focus their efforts and with whom researchers ought to be engaging reveal three distinct ways of approaching health inequalities, each of which has its own epistemological foundations. Such differences imply that a consensus on reducing health inequalities is unlikely to materialise. Instead, progress seems most likely if all three approaches are simultaneously enabled

The White/Black Educational Gap, Stalled Progress, and the Long Term Consequences of the Crack Epidemic

We propose the rise of crack cocaine as an explanation for the end to the convergence in black-white educational outcomes beginning in the mid-1980s. After constructing a measure of the arrival of crack arrival in cities and states, we first show there are large increases in incarceration and murder rates after the arrival of the drug. We show that the emergence of crack accounts for between 39 and 71 percent of the fall in black male high school graduation rates. The results suggest that, in line with human capital theory, educational investments declined in response to decreased returns to schooling