The effect of sertraline, haloperidol and apomorphine on the behavioural manipulation of slugs (Deroceras invadens) by the nematode Phasmarhabditis hermaphrodita

The nematode Phasmarhabditis hermaphrodita can infect and kill many species of slugs and has been formulated into a biological control agent for farmers and gardeners. P. hermaphrodita can manipulate the behaviour of slugs, making those infected move to areas where the nematode is present. Research suggests P. hermaphrodita uses manipulation of biogenic amines to achieve this, however the exact role of serotonin and dopamine needs further elucidation. Here we fed slugs Deroceras invadens (uninfected and infected with P. hermaphrodita) apomorphine, sertraline and haloperidol and observed their behaviour when given a choice between a P. hermaphrodita infested habitat, or a parasite free area of soil. In contrast to their usual P. hermaphrodita avoidance behaviour, uninfected D. invadens fed sertraline were attracted to the nematodes and conversely those fed haloperidol avoided the nematodes. D. invadens fed apomorphine were recorded equally on the control and nematode side. D. invadens pre-infected with P. hermaphrodita fed sertraline and apomorphine were found significantly more on the side with the nematodes. However, suppressing dopaminergic signalling through feeding with haloperidol abrogated this attraction and slugs were found on both sides. These results demonstrate that serotonin and dopamine are important potential regulators of behavioural manipulation by P. hermaphrodita

Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain

© Copyright © 2019 Naylor, Hesam-Shariati, McAuley, Boag, Newton-John, Rae and Gustin. A decrease in glutamate in the medial prefrontal cortex (mPFC) has been extensively found in animal models of chronic pain. Given that the mPFC is implicated in emotional appraisal, cognition and extinction of fear, could a potential decrease in glutamate be associated with increased pessimistic thinking, fear and worry symptoms commonly found in people with chronic pain? To clarify this question, 19 chronic pain subjects and 19 age- and gender-matched control subjects without pain underwent magnetic resonance spectroscopy. Both groups also completed the Temperament and Character, the Beck Depression and the State Anxiety Inventories to measure levels of harm avoidance, depression, and anxiety, respectively. People with chronic pain had significantly higher scores in harm avoidance, depression and anxiety compared to control subjects without pain. High levels of harm avoidance are characterized by excessive worry, pessimism, fear, doubt and fatigue. Individuals with chronic pain showed a significant decrease in mPFC glutamate levels compared to control subjects without pain. In people with chronic pain mPFC glutamate levels were significantly negatively correlated with harm avoidance scores. This means that the lower the concentration of glutamate in the mPFC, the greater the total scores of harm avoidance. High scores are associated with fearfulness, pessimism, and fatigue-proneness. We suggest that chronic pain, particularly the stress-induced release of glucocorticoids, induces changes in glutamate transmission in the mPFC, thereby influencing cognitive, and emotional processing. Thus, in people with chronic pain, regulation of fear, worry, negative thinking and fatigue is impaired

Corrigendum: Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain.

[This corrects the article DOI: 10.3389/fneur.2019.01110.]

Corrigendum: Reduced Glutamate in the Medial Prefrontal Cortex Is Associated With Emotional and Cognitive Dysregulation in People With Chronic Pain(Front. Neurol., (2019), 10, (1110), 10.3389/fneur.2019.01110)

In the original article, there was an error in the Author Contributions. It has been updated to align with the guidelines of the International Committee of Medical Journal Editors. A correction has been made to the Author Contributions

Increased serum levels of TGFβ1 in children with localized scleroderma

scleroderm

Evaluation of Serious Infection in Pediatric Patients with Low Immunoglobulin Levels Receiving Rituximab for Granulomatosis with Polyangiitis or Microscopic Polyangiitis

Introduction: The aim of this work was to assess the impact of prolonged low immunoglobulin (IgG or IgM) serum concentrations on the potential cumulative serious infection (SI) risk in pediatric patients following rituximab treatment for granulomatosis with polyangiitis or microscopic polyangiitis (GPA/MPA) in PePRS. Methods: Patients aged ≥ 2 to < 18 years received four weekly intravenous rituximab infusions of 375 mg/m2 and concomitant glucocorticoid taper. After 6 months, patients could receive further rituximab and/or other immunosuppressants per investigator discretion. Immunoglobulin levels and SIs were assessed throughout the 4.5-year observation period. Prolonged low IgG or IgM was defined as below the lower limit of normal age-specific reference range for ≥ 4 months. Results: A total of 25 patients were included, of whom 19 (76%) had GPA and six (24%) had MPA; 18 (72%) had newly diagnosed disease and seven (28%) had relapsing disease. All 25 patients completed the rituximab induction regimen; 24 completed ≥ 18 months of follow-up. At month 18, eighteen patients (72%) had prolonged low IgG; 19 (76%), prolonged low IgM; and 15 (60%), both. Seven patients (28%) had nine SIs; one occurred during or after prolonged low IgG only, two during or after prolonged low IgM only, and six during or after concurrent prolonged low IgG and IgM. No patients died or discontinued the study due to SI. All patients had complete and sustained peripheral B-cell depletion for ≥ 6 months. Conclusions: The majority of pediatric patients who received rituximab for GPA/MPA with prolonged low immunoglobulin levels did not experience SIs. In patients with SIs, these events were manageable, and the number of SIs did not increase over time or with multiple rituximab treatments. These observations are consistent with the rituximab safety profile in adults with GPA/MPA. Trial registration: ClinicalTrials.gov identifier, NCT01750697

The effects of district magnitude and social diversity on party system fragmentation in majoritarian systems

Cross-national models of party system fragmentation hold that social diversity and district magnitude interact: higher levels of district magnitude allow for greater expression of social diversity that leads to higher levels of party system fragmentation. Most models, however, ignore differences between majoritarian and proportional electoral rules, which may significantly alter the impact of district magnitude, as well as the way in which district magnitude impacts the translation of social cleavages into party system fragmentation. Examining the case of Singapore suggests majoritarian multimember districts limit party system fragmentation, particularly by reducing the degree to which ethnic and religious diversity are translated into political parties. Applying these insights to a standard cross-national model of party system fragmentation, the results suggest that majoritarian multimember districts produce lower levels of party system fragmentation than proportional multimember districts.

A nematode that can manipulate the behaviour of slugs

The ability of parasites to manipulate the behaviour of their hosts has evolved multiple times, and has a clear fitness benefit to the parasite in terms of facilitating growth, reproduction and transfer to suitable hosts. The mechanisms by which these behavioural changes are induced are poorly understood, but in many cases parasite manipulation of serotonergic signalling in the host brain is implicated. Here we report that Phasmarhabditis hermaphrodita, a parasite of terrestrial gastropod molluscs, can alter the behaviour of slugs. Uninfected slugs (Deroceras panormitanum, Arion subfuscus and Arion hortensis) avoid areas where P. hermaphrodita is present, but slugs infected with P. hermaphrodita are more likely to be found where the nematodes are present. This ability is specific to P. hermaphrodita and other nematodes (Steinernema carpocapsae and Heterorhabditis bacteriophora) do not induce this behavioural change. To investigate how P. hermaphrodita changes slug behaviour we exposed slugs to fluoxetine (a selective serotonin reuptake inhibitor) and cyproheptadine (a serotonin receptor antagonist). Uninfected slugs fed fluoxetine no longer avoided areas where P. hermaphrodita was present; and conversely, infected slugs fed cyproheptadine showed no increased attraction to areas with nematodes. These findings suggest that a possible mechanism by which P. hermaphrodita is able to manipulate parasite avoidance behaviour in host slugs is by manipulating serotonergic signalling in the brain, and that increased serotonin levels are potentially associated with a reduction in parasite avoidance