Studies investigating peripherial blood derived cells that express the high affinity receptor for immunoglobulin E (FceRI) in allergic disorders

It is just forty years since the identification of immunoglobulin E (IgE) as the reagin responsible for allergen induced immediate hypersensitivity reactions. IgE exerts its biological actions through the binding of its Fc fragment to specific Fc receptors on effector cells. There are two predominant Fc receptors for IgE – Fc?RI, which has a very high affinity for IgE and Fc?RII, which shows less avid binding. For much of the first two decades after the identification of IgE, it was thought that Fc?RI expression was limited to mast cells and basophils and that IgE binding to other cell types such as Blymphocytes and antigen presenting cells (APCs) was mainly due to Fc?RII . However with major advances in characterisation and functional knowledge of Fc?RI, particularly in the last fifteen years, it has become apparent that Fc?RI can be expressed on several more cell types that may be involved in initiation and maintenance of allergic inflammation – including APCs (monocytes and dendritic cells) and possibly eosinophils.The research described in the four papers forming this thesis was completed during this period and evaluated Fc?RI expression on different cell types, their potential roles in allergen induced inflammatory responses and whether successful therapeutic strategies for allergic disorders may involve actions on Fc?RI+ cells. The relative expression of Fc?RI on peripheral blood basophils, monocytes and eosinophils from atopic and non-atopic subjects and any relationship with serum IgE concentrations was assessed in the first paper. The second study examined a potentially important role for basophils as a cellular source of rapidly releasable IL-4 which may help initiate allergen induced TH2 responses. The next study investigated the possible effects on allergen induced early and late asthmatic responses of the immunosuppressive drug cyclosporin A which had been shown both to inhibit mast cell and basophil degranulation and cytokine secretion (particularly by CD4+ T-cells). The final study evaluated Fc?RI expression on these cell types as well humoral factors (e.g. seasonal changes in allergen specific IgG and IgE) in subjects who, after 3 to 4 years of grass pollen immunotherapy, had continued on either active or placebo immunotherapy for a further 3 years.A historical perspective explaining some of the reasons the studies were done is provided in the introductory chapter whilst the discussion chapter at the end reviews how many of the findings of the study have evolved in subsequent years right up to the present day and finishes off with a brief synopsis of how rapidly increasing knowledge of the regulatory functions of dendritic cells (expressing Fc?RI and often monocyte derived) has resulted in better understanding of the mechanisms of allergen specific immunotherapy and is leading to more effective treatment modalities

Sleep duration and mood

It is widely believed that sleep and mood are interrelated and that prolongation of sleep may have beneficial effects on subsequent mood and general well-being. In the present investigation, it is hypothesised that excess sleep is in fact, detrimental to mood and is associated with a 'Wornout Syndrome', characterised by feelings of fatigue and lethargy, that can persist for up to 5 hours. The studies to be presented here compare the differential effects of Sleep Extension and Sleep Restriction on mood in healthy adults. The experimental design required subjects to undergo one night of Sleep Extension [+2h] and, following an interval of one-week, one night of Sleep Reduction [-2h]. The conditions were counterbalanced. Subjective assessments were conducted hourly on mood states and sleepiness using an adapted Profile of Mood States Questionnaire and the Stanford Sleepiness Scale. Actometers were worn throughout the experimental days and nights. In the first study of 10 subjects results indicated that four subjects were adversely affected by oversleep. Study 2 investigated the effects of sleep duration on mood in 20 healthy adults. Personality factors were assessed using Cattell's 16PF Questionnaire. Subjects maintaining regular sleep schedules reported negative effects of oversleep on subsequent mood. Results indicated that certain personality types were predisposed to the 'Wornout Syndrome' following Sleep Extension. In Study 3, thirty-four subjects were selected on the basis of personality type. It was hypothesised that Introverts, Morning types, Emotionally Tenderminded and Low Impulsives would report symptoms characteristic of the 'Wornout Syndrome' following one night of Sleep Extension. This was confirmed by reports of increased fatigue, diminished vigor, and increased confusion following Sleep Extension. Oversleeping produced greater detrimental effects on mood than a comparable reduction in sleep duration. There are many similarities in symptomatology between the 'Wornout Syndrome' and Chronic Fatigue Syndrome (CFS), specifically, intense fatigue and impaired concentration. Interestingly, chronically fatigued patients often complain of sleep disturbance, and spend much of their time resting in bed. It was hypothesised that the 'Wornout Syndrome' may be a confounding factor in the symptomatology of CFS. As a clinical dimension, twelve subjects were investigated polysomnographically [six were CFS patients]. Findings indicated that CFS patients acquired sleep of longer duration than controls. In addition to excess nocturnal sleep, CFS patients were taking daytime naps. EEG data indicated that these individuals obtained twice the normal amount of slow wave sleep. CFS sufferers may be better advised to regulate their sleep habits and reduce their total sleep time to avoid the confounding effects of the 'Wornout Syndrome'

What research tells us about the avocado toast controversy

Contrary to what the Australian tycoon says, consuming 'luxury' goods plays a key role for deprived individuals, write Clement Bellet and Eve Sihr

Integrating vitrinite reflectance, rock-eval pyrolysis, flourescence microscopy and palynology of the Athabasca oil sands, Kearl Lake area, northeastern Alberta

Three cores from the Kearl Lake Oil Sands area within the Athabasca deposit of northeastern Alberta have been analyzed to understand the thermal history of the McMurray and Clearwater formations of the Lower Cretaceous Mannville Group. The approach involves the integration of vitrinite reflectance (VR), Rock-Eval pyrolysis, fluorescence microscopy, and palynology. Mean VR varies between 0.21 and 0.43% Ro and indicates thermally immature levels equivalent to the rank of lignite to sub-bituminous coal. Although differing lithologies have influenced VR to some extent (i.e., coals and bitumen-rich zones), groundwater influence and oxidation seem not to have measurably altered YR. Rock-Eval analysis points to Type III/IV kerogen, and samples rich in amorphous organic matter (ADM) show little to no fluorescence characteristics, implying a terrestrial source of origin. Palynology reveals the presence of some delicate macerals but lack of fluorescence and abundant ADM suggests some degradation and partial oxidation of the samples

Grounding Characters and Places in Narrative Texts

Tracking characters and locations throughout a story can help improve the understanding of its plot structure. Prior research has analyzed characters and locations from text independently without grounding characters to their locations in narrative time. Here, we address this gap by proposing a new spatial relationship categorization task. The objective of the task is to assign a spatial relationship category for every character and location co-mention within a window of text, taking into consideration linguistic context, narrative tense, and temporal scope. To this end, we annotate spatial relationships in approximately 2500 book excerpts and train a model using contextual embeddings as features to predict these relationships. When applied to a set of books, this model allows us to test several hypotheses on mobility and domestic space, revealing that protagonists are more mobile than non-central characters and that women as characters tend to occupy more interior space than men. Overall, our work is the first step towards joint modeling and analysis of characters and places in narrative text.Comment: 12 pages, 4 figures, 5 tables; to appear in the proceedings of ACL 202

Presynaptic kainate receptor-mediated facilitation of glutamate release involves Ca2+–calmodulin and PKA in cerebrocortical synaptosomes

AbstractWe have explored the mechanisms involved in the facilitation of glutamate release mediated by the activation of kainate receptors (KARs) in the cortex using isolated nerve terminals (synaptosomes). Kainate (KA) produced an increase on glutamate release at 100μM. The effect of KA was antagonized by NBQX (with AMPA receptors blocked by GYKI53655). This facilitation was suppressed by the inhibition of PKA activation by Rp-Br-cAMP and H-89. Moreover, the facilitation of glutamate release mediated by KAR requires the mobilization of intrasynaptosomal Ca2+ stores and the formation of a Ca2+–calmodulin complex. We conclude that KARs present on presynaptic terminals in the neocortex mediate the facilitation of glutamate release through a mechanism involving an increase in cytosolic Ca2+ to activate a Ca2+–calmodulin–AC/cAMP/PKA signaling cascade

Kainate Receptors: Role in Epilepsy

Kainate (KA) is a potent neurotoxin that has been widely used experimentally to induce acute brain seizures and, after repetitive treatments, as a chronic model of temporal lobe epilepsy (TLE), with similar features to those observed in human patients with TLE. However, whether KA activates KA receptors (KARs) as an agonist to mediate the induction of acute seizures and/or the chronic phase of epilepsy, or whether epileptogenic effects of the neurotoxin are indirect and/or mediated by other types of receptors, has yet to be satisfactorily elucidated. Positing a direct involvement of KARs in acute seizures induction, as well as a direct pathophysiological role of KARs in the chronic phase of TLE, recent studies have examined the specific subunit compositions of KARs that might underly epileptogenesis. In the present mini-review, we discuss the use of KA as a convulsant in the experimental models of acute seizures of TLE, and consider the involvement of KARs, their subunit composition and the mode of action in KAR-mediated epilepsy. In acute models, evidence points to epileptogenesis being precipitated by an overall depression of interneuron GABAergic transmission mediated by GluK1 containing KARs. On glutamatergic principal cell in the hippocampus, GluK2-containing KARs regulate post-synaptic excitability and susceptibility to KA-mediated epileptogenesis. In chronic models, a role GluK2-containing KARs in the hippocampal CA3 region provokes limbic seizures. Also observed in the hippocampus, is a ‘reactive plasticity’, where MF sprouting is seen with target granule cells at aberrant synapses recruiting de novo GluR2/GluR5 heteromeric KARs. Finally, in human epilepsy and animal models, astrocytic expression of GluK1, 2, 4, and 5 is reported

Non-canonical Mechanisms of Presynaptic Kainate Receptors Controlling Glutamate Release

A metabotropic modus operandi for kainate receptors (KARs) was first discovered in 1998 modulating GABA release. These receptors have been also found to modulate glutamate release at different synapses in several brain regions. Mechanistically, a general biphasic mechanism for modulating glutamate release by presynaptic KARs with metabotropic actions has emerged, with low KA concentrations invoking an increase in glutamate release, whereas higher concentrations of KA mediate a decrease in the release of this neurotransmitter. The molecular mechanisms underpinning the opposite modulation of glutamate release are distinct, with a G-protein-independent, adenylate cyclase (AC)- and protein kinase A (PKA)-dependent mechanism mediating the facilitation of glutamate release, while a G-protein dependent mechanism (with or without protein kinase recruitment) is involved in the decrease of neurotransmitter release. In the present review, we revisit the mechanisms underlying the non-canonical modus operandi of KARs effecting the bimodal control of glutamatergic transmission in different brain regions, and address the possible functions that this modulation may support

Introduction to Dry Gas Seals and Systems

TutorialDry gas seals are used as low-leakage shaft end seals for many centrifugal compressors and other turbomachines. This short course provides a comprehensive overview of sealing system and dry gas seals in various turbomachinery applications, addressing multiple topics ranging from fundamentals to detailed design considerations for reliable operation. A course attendee can expect a greater understanding of technologies, failure modes, and requirements for components in dry gas seals and seal supply/vent systems, with perspectives from an end user, a seal manufacturer, and a research organization.This short course will give listeners a thorough understanding of dry gas seals, including design, operation, and maintenance. Starting with the background of how dry gas seals were developed as a response to issues with wet seals, the course will then move into a detailed discussion on seal design. The instructors will explain how each component of the seal contributes to its operation and issues that can arise if parts are selected incorrectly. Next, seal selection for various applications (pipeline, process, advanced applications) will be discussed. Methods for seal testing to ensure that design conditions are met will be described, including test rigs studying off-design conditions, such as transients or contaminant injection.The gas conditioning process can be critical to successful seal operation, so seal gas panels and their components will be discussed in great detail. Operation during transients can be particularly challenging, so panel considerations specific to transient operation will be discussed. The recently-released API 692 will be discussed as it pertains to dry gas seal panel design, seal requirements, and seal testing.Understanding common failure modes is an important step to improving dry gas seal reliability. Recent research on dry gas seal failures will be presented, including failure statistics and failure modes. Insight on failure modes specific to heat generation from liquid contamination will be discussed, and recommendations will be provided to reduce failures.Copyright© 2020 by Turbomachinery Laboratory, Texas A&M Engineering Experiment StationThis short course is aimed primarily at end users, but the multifaceted approach (end user, OEM, research) will provide a valuable perspective on dry gas seals to anyone in the rotating equipment industry. By the end of the course, attendees will have a detailed understanding of dry gas seals and their associated systems