Changes in lipophorins are related to the activation of phenoloxidase in the haemolymph of Locusta migratoria in response to injection of immunogens

In Locusta migratoria, activation of phenoloxidase in the haemolymph in response to injection of laminarin is age-dependent: being absent in fifth instar nymphs and newly emerged adults, and only becoming evident four days after the final moult. This pattern of change in phenoloxidase activation correlates with the pattern of change in the concentration of apolipophorin-III (apoLp-III) in the haemolymph. Injection of a conspecific adipokinetic hormone (Lom-AKH-I) has no effect on the phenoloxidase response in nymphs or newly emerged adults but, in adults older than four days, co-injection of the hormone with laminarin prolongs the activation of phenoloxidase in the haemolymph: a similar enhancement of the response to laminarin is observed in locusts that have been starved for 48 h but not injected with AKH-I. During most of the fifth stadium, injection of laminarin results in a decrease in the level of prophenoloxidase in the haemolymph; an effect that is not observed in adults of any age. Marked changes in the concentration of apoLp-III, and the formation of LDLp in the haemolymph, are observed after injection of laminarin (or LPS) and these are remarkably similar, at least qualitatively, to those that occur after injection of AKH-I. The involvement of lipophorins in the activation of locust prophenoloxidase in response to immunogens is discussed

Induced hyperlipaemia and immune challenge in locusts

Injections of immunogens, such as β-1,3-glucan or lipopolysaccharide (LPS), bring about a marked hyperlipaemia with associated changes in lipophorins and apolipophorin-III in the haemolymph of Locusta migratoria. These changes are similar to those observed after injection of adipokinetic hormone (AKH). The possibility that endogenous AKH is released as part of the response to these immunogens is investigated using passive immunisation against AKH-I, and measurement of AKH-I titre in the haemolymph after injection of immunogens. The data presented show that, despite the similarity of the changes brought about by the presence of immunogens in the haemolymph to those brought about by AKH, there is no release of endogenous AKH after injection of laminarin or LPS. A direct effect of the immunogens on release of neutral lipids by the fat body cannot be demonstrated in vitro, and the mechanism by which hyperlipaemia is induced during immune challenge remains uncertain

Interactions between the endocrine and immune systems in locusts

The prophenoloxidase cascade in the haemolymph of mature adult Locusta migratoria migratorioides (R & F) is activated in response to injection of laminarin, a -1,3 glucan. Co-injection of adipokinetic hormone-I (Lom-AKH-I) and laminarin prolongs the activation of the enzyme in a dose-dependent manner. However, injections of bacterial lipopolysaccharide (LPS) do not activate prophenoloxidase unless AKH is co-injected, when there is a dose-dependent increase in the level of phenoloxidase that persists in the haemolymph for several hours. Even when AKH is co-injected, the highest levels of phenoloxidase activity are always greater after injection of laminarin than after LPS, and these two immunogens must activate the prophenoloxidase cascade by quite distinct pathways. In the present study, interactions between the endocrine and immune systems were examined with respect to activation of prophenoloxidase and the formation of nodules: injection of LPS induces nodule formation in adult locusts. With LPS from Pseudomonas aeruginosa, nodules form exclusively in dense accumulations in the anterior portion of the abdomen on either side of the dorsal blood vessel associated with the dorsal diaphragm. However, with LPS from Escherichia coli, fewer nodules are formed but with a similar distribution, except that occasionally some nodules are aligned additionally on either side of the ventral nerve cord. Co-injection of Lom-AKH-I with LPS from either bacteria stimulates greater numbers of nodules to be formed. This effect of coinjection of AKH on nodule formation is seen at low doses of hormone with only 0.3 or 0.4 pmol of Lom-AKH-1, respectively, increasing the number of nodules by 50%. Injections of octopamine or 5-hydroxytryptamine do not mimic either of the actions of Lom-AKH-I described here. Co-injection of an angiotensin-converting enzyme inhibitor, captopril, reduces nodule formation in response to injections of LPS but has no effect on the activation of phenoloxidase. Co-injection of an inhibitor of eicosanoid synthesis, dexamethasone, with LPS influences nodule formation (with or without AKH) in different ways according to the dose of dexamethasone used, but does not affect activation of prophenoloxidase. Eicosanoid synthesis is important for nodule formation, but not for the activation of the prophenoloxidase cascade in locust haemolymph

Adding to the Family of Copper Complexes Featuring Borohydride Ligands Based on 2-Mercaptopyridyl Units

Borohydride ligands featuring multiple pendant donor functionalities have been prevalent in the chemical literature for many decades now. More recent times has seen their development into new families of so-called soft scorpionates, for example, those featuring sulfur based donors. Despite all of these developments, those ligands containing just one pendant group are rare. This article explores one ligand family based on the 2-mercaptopyridine heterocycle. The coordination chemistry of the monosubstituted ligand, [H3B(mp)]− (mp = 2-mercaptopyridyl), has been explored. Reaction of Na[BH3(mp)] with one equivalent of Cu(I)Cl in the presence of either triphenylphosphine or tricyclohexylphosphine co-ligands leads to the formation of [Cu{H3B(mp)}(PR3)] (R = Ph, 1; Cy, 2), respectively. Structural characterization confirms a κ3-S,H,H coordination mode for the borohydride-based ligand within 1 and 2, involving a dihydroborate bridging interaction (BH2Cu) with the copper centers

The misuses of sustainability: adult education, citizenship and the dead hand of neoliberalism

‘‘Sustainability’’ has a captivating but disingenuous simplicity: its meanings are complex, and have political and policy significance. Exploring the application of the term to adult education, this paper argues that a particular discourse of ‘‘sustainability’’ has become a common-sense, short-circuiting critical analysis and understanding of policy options. This ‘‘business discourse’’ of sustainability, strongly influenced by neoliberal ideas, encourages the presumption that educational programmes and movements which have died out were unsustainable, bound to fail, and even responsible – having failed to adapt – for their own demise. Potentially valuable experience is thus excluded from the educational policy canon. The author uses three cases from 20th-century adult education, namely (1) English liberal adult education; (2) ‘‘mass education’’, also known as community development, in the British colonies; and (3) UNESCO’s Fundamental Education, to challenge this presumption. He demonstrates for each case how a business discourse has implied their ‘‘unsustainability’’, but that the reality was more complex and involved external political intervention

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Locusts as model organisms in which to study immunogen-induced anorectic behaviour

When injected into adult or nymphal Locusta that have been deprived of food for 2 h, immunogens such as laminarin and bacterial LPS can induce an almost immediate dose-dependent state of anorexia for at least 1 h. Such anorexia is a component of a medley of physiological and behavioural changes called collectively 'sickness behaviour' that occurs in a wide range of animals in response to infection or immune challenge. Sub-optimal amounts of injected laminarin allow some locusts to feed, but with a longer latency than in controls, although the length of the first meal is unaffected. The feeding behaviour of fifth instar nymphs is more sensitive to laminarin than that of adults, but both stages respond to amounts of immunogen that are lower than those required to activate the phenoloxidase cascade. Injection of adipokinetic hormone (AKH) before the period of food deprivation prevents the anorexigenic action of the laminarin in adults but not in nymphs. It is argued that the effect of the AKH may be indirect, through its lipid-mobilising action. The insecticide pymetrozine increases the latency to feed but also reduces the length of the first meal, and its anorexigenic activity is not affected by injection of AKH. The present data support the concept that laminarin-induced anorexia involves a central lack of motivation to eat, rather than a 'stop eating' signal. Others have shown that the mechanism of action of pymetrozine involves the serotonergic system and can be blocked by mianserin, so it is intriguing that in the present study injection of mianserin prior to that of laminarin modulates the anorexigenic effect of the immunogen. This suggests that biogenic amines are involved in the control of appetitive behaviour in locusts, as they are in vertebrates. The possible usefulness of the locust model in studying sickness-induced anorexia is discussed briefly