Hearing voices

As the director of Miles Away from “The Cool,” the performer asks me to listen to/for the implications of specific location, the pedagogical potentiality in the life and work of Miles Davis, and his relationship with Davis. The performer asks the audience to consider their subject positions and relationships to and with race, cultural icons, and their pedagogical practices as students and teachers. Together, we want to create a performance that invites the audience to exercise performative reflexivity and listen dialogically. This essay is the director\u27s reflection of this process

Muscarinic Acetylcholine Type 1 Receptor Activity Constrains Neurite Outgrowth by Inhibiting Microtubule Polymerization and Mitochondrial Trafficking in Adult Sensory Neurons

The muscarinic acetylcholine type 1 receptor (M1R) is a metabotropic G protein-coupled receptor. Knockout of M1R or exposure to selective or specific receptor antagonists elevates neurite outgrowth in adult sensory neurons and is therapeutic in diverse models of peripheral neuropathy. We tested the hypothesis that endogenous M1R activation constrained neurite outgrowth via a negative impact on the cytoskeleton and subsequent mitochondrial trafficking. We overexpressed M1R in primary cultures of adult rat sensory neurons and cell lines and studied the physiological and molecular consequences related to regulation of cytoskeletal/mitochondrial dynamics and neurite outgrowth. In adult primary neurons, overexpression of M1R caused disruption of the tubulin, but not actin, cytoskeleton and significantly reduced neurite outgrowth. Over-expression of a M1R-DREADD mutant comparatively increased neurite outgrowth suggesting that acetylcholine released from cultured neurons interacts with M1R to suppress neurite outgrowth. M1R-dependent constraint on neurite outgrowth was removed by selective (pirenzepine) or specific (muscarinic toxin 7) M1R antagonists. M1R-dependent disruption of the cytoskeleton also diminished mitochondrial abundance and trafficking in distal neurites, a disorder that was also rescued by pirenzepine or muscarinic toxin 7. M1R activation modulated cytoskeletal dynamics through activation of the G protein (Gα13) that inhibited tubulin polymerization and thus reduced neurite outgrowth. Our study provides a novel mechanism of M1R control of Gα13 protein-dependent modulation of the tubulin cytoskeleton, mitochondrial trafficking and neurite outgrowth in axons of adult sensory neurons. This novel pathway could be harnessed to treat dying-back neuropathies since anti-muscarinic drugs are currently utilized for other clinical conditions

Experiences of hearing voices: analysis of a novel phenomenological survey

Background: Auditory hallucinations—or voices—are a common feature of many psychiatric disorders and are also experienced by individuals with no psychiatric history. Understanding of the variation in subjective experiences of hallucination is central to psychiatry, yet systematic empirical research on the phenomenology of auditory hallucinations remains scarce. We aimed to record a detailed and diverse collection of experiences, in the words of the people who hear voices themselves. Methods: We made a 13 item questionnaire available online for 3 months. To elicit phenomenologically rich data, we designed a combination of open-ended and closed-ended questions, which drew on service-user perspectives and approaches from phenomenological psychiatry, psychology, and medical humanities. We invited people aged 16–84 years with experience of voice-hearing to take part via an advertisement circulated through clinical networks, hearing voices groups, and other mental health forums. We combined qualitative and quantitative methods, and used inductive thematic analysis to code the data and χ2 tests to test additional associations of selected codes. Findings: Between Sept 9 and Nov 29, 2013, 153 participants completed the study. Most participants described hearing multiple voices (124 [81%] of 153 individuals) with characterful qualities (106 [69%] individuals). Less than half of the participants reported hearing literally auditory voices—70 (46%) individuals reported either thought-like or mixed experiences. 101 (66%) participants reported bodily sensations while they heard voices, and these sensations were significantly associated with experiences of abusive or violent voices (p=0·024). Although fear, anxiety, depression, and stress were often associated with voices, 48 (31%) participants reported positive emotions and 49 (32%) reported neutral emotions. Our statistical analysis showed that mixed voices were more likely to have changed over time (p=0·030), be internally located (p=0·010), and be conversational in nature (p=0·010). Interpretation: This study is, to our knowledge, the largest mixed-methods investigation of auditory hallucination phenomenology so far. Our survey was completed by a diverse sample of people who hear voices with various diagnoses and clinical histories. Our findings both overlap with past large-sample investigations of auditory hallucination and suggest potentially important new findings about the association between acoustic perception and thought, somatic and multisensorial features of auditory hallucinations, and the link between auditory hallucinations and characterological entities

Calcium signalling in sensory neurones and peripheral glia in the context of diabetic neuropathies

© 2014 Elsevier Ltd. Peripheral sensory nervous system is comprised of neurones with their axons and neuroglia that includes satellite glial cells in sensory ganglia, myelinating, non-myelinating and perisynaptic Schwann cells. Pathogenesis of peripheral diabetic polyneuropathies is associated with aberrant function of both neurones and glia. Deregulated Ca2+ homoeostasis and aberrant Ca2+ signalling in neuronal and glial elements contributes to many forms of neuropathology and is fundamental to neurodegenerative diseases. In diabetes both neurones and glia experience metabolic stress and mitochondrial dysfunction which lead to deregulation of Ca2+ homeostasis and Ca2+ signalling, which in their turn lead to pathological cellular reactions contributing to development of diabetic neuropathies. Molecular cascades responsible for Ca2+ homeostasis and signalling, therefore, can be regarded as potential therapeutic targets

Inner speech and clarity of self-concept in thought disorder and auditory-verbal hallucinations

Eighty patients and thirty controls were interviewed using one interview that promoted personal disclosure and another about everyday topics. Speech was scored using the Thought, Language and Communication scale (TLC). All participants completed the Self-Concept Clarity Scale (SCCS) and the Varieties of Inner Speech Questionnaire (VISQ). Patients scored lower than comparisons on the SCCS. Low scores were associated the disorganized dimension of TD. Patients also scored significantly higher on condensed and other people in inner speech, but not on dialogical or evaluative inner speech. The poverty of speech dimension of TD was associated with less dialogical inner speech, other people in inner speech, and less evaluative inner speech. Hallucinations were significantly associated with more other people in inner speech and evaluative inner speech. Clarity of self-concept and qualities of inner speech are differentially associated with dimensions of TD. The findings also support inner speech models of hallucinations

Long-term and trans-generational effects of neonatal experience on sheep behaviour

Early life experiences can have profound long-term, and sometimes trans-generational, effects on individual phenotypes. However, there is a relative paucity of knowledge about effects on pain sensitivity, even though these may impact on an individual's health and welfare, particularly in farm animals exposed to painful husbandry procedures. Here, we tested in sheep whether neonatal painful and non-painful challenges can alter pain sensitivity in adult life, and also in the next generation. Ewes exposed to tail-docking or a simulated mild infection (lipopolysaccharide (LPS)) on days 3–4 of life showed higher levels of pain-related behaviour when giving birth as adults compared with control animals. LPS-treated ewes also gave birth to lambs who showed decreased pain sensitivity in standardized tests during days 2–3 of life. Our results demonstrate long-term and trans-generational effects of neonatal experience on pain responses in a commercially important species and suggest that variations in early life management can have important implications for animal health and welfare

RAFT dispersion polymerization of N,N-dimethylacrylamide in a series of n-alkanes using a thermoresponsive poly(tert-octyl acrylamide) steric stabilizer

Herein we report the reversible addition–fragmentation chain transfer (RAFT) solution polymerization of tert-octyl acrylamide (OAA) in 1,4-dioxane using a trithiocarbonate-based RAFT agent. POAA homopolymers were synthesized with good control (Mw/Mn < 1.22) within 1 h at 70 °C when targeting mean degrees of polymerization (DP) of up to 100. Differential scanning calorimetry studies conducted on a series of five POAA homopolymers indicated a weak molecular weight dependence for the glass transition temperature (Tg), which varied from 67 to 83 °C for POAA DPs ranging from 22 to 99. High blocking efficiencies were observed when chain-extending such homopolymers with OAA, suggesting that most of the RAFT end-groups remain intact. Subsequently, we employed POAA as a steric stabilizer block for the PISA syntheses of spherical nanoparticles in n-heptane via RAFT dispersion polymerization of N,N-dimethylacrylamide (DMAC) at 70 °C. Targeting PDMAC DPs between 50 and 250 resulted in reasonably good control (Mw/Mn ≤ 1.42) and produced well-defined spherical diblock copolymer nanoparticles (z-average diameters ranging from 23 nm to 91 nm, with DLS polydispersities remaining below 0.10) within 5 h. A facile one-pot synthesis route to near-monodisperse 36 nm diameter POAA82-PDMAC100 nanoparticles was developed in n-heptane that provided similar control over the molecular weight distribution (Mw/Mn = 1.19). Unfortunately, POAA85-PDMACx diblock copolymer nanoparticles tended to deform and undergo film formation prior to transmission electron microscopy (TEM) studies. To overcome this problem, ethylene glycol diacrylate (EGDA) was introduced towards the end of the DMAC polymerization. The resulting core-crosslinked POAA85-PDMAC195-PEGDA20 triblock copolymer nano-objects exhibited a relatively well-defined spherical morphology. Interestingly, the colloidal stability of POAA85-PDMACx diblock copolymer dispersions depends on the type of n-alkane. Spherical nanoparticles produced in n-heptane or n-octane remained colloidally stable on cooling to 20 °C. However, the colloidally stable POAA-PDMAC nanoparticles prepared at 70 °C in higher n-alkanes became flocculated on cooling. This is because the POAA steric stabilizer chains exhibit upper critical solution temperature (UCST)-type behavior in such solvents. Nanoparticle aggregation was characterized by variable temperature turbidimetry and dynamic light scattering experiments

Synthesis and characterization of waterborne pyrrolidone-functional diblock copolymer nanoparticles prepared via surfactant-free RAFT emulsion polymerization

Polymerization-induced self-assembly enables the facile synthesis of a wide range of block copolymer nano-objects in the form of concentrated dispersions. In this context, many surfactant-free reversible addition–fragmentation chain transfer (RAFT) aqueous emulsion polymerization formulations have been reported using various nonionic and polyelectrolytic water-soluble precursors for the steric stabilizer block. In the present study, we examine poly(2-(N-acryloyloxy)ethyl pyrrolidone) (PNAEP) as a new nonionic stabilizer block. A trithiocarbonate-based PNAEP precursor with a mean degree of polymerization of 67 was employed as the steric stabilizer for the RAFT emulsion polymerization of styrene, n-butyl acrylate (nBA), or statistical mixtures thereof. The RAFT emulsion polymerization of styrene using a VA-044 azo initiator at 80 °C and pH 7 led to essentially full conversion within 40 min, with induction times as short as 10 min, whereas gel permeation chromatography analysis confirmed efficient chain extension and relatively low dispersities (Mw/Mn < 1.30). Dynamic light scattering (DLS) studies indicated that systematically increasing the target degree of polymerization (DP) from 100 to 700 enabled the z-average diameter of the resulting kinetically trapped spherical nanoparticles to be varied from 55 to 156 nm. The same PNAEP67 precursor was then employed for the RAFT emulsion polymerization of nBA at 30 °C using a low-temperature redox initiator at pH 3. More than 99% conversion was achieved within 25 min, and efficient chain extension was observed up to a target DP of 700. However, relatively broad molecular weight distributions (Mw/Mn = 1.38–1.64) were obtained, presumably owing to side reactions such as chain transfer to polymer. DLS studies indicated that a series of kinetically-trapped PNAEP67–PnBAx spheres (where x = 100–700) exhibited z-average diameters ranging from 45 to 141 nm. Attempts to use this low-temperature initiator protocol for the homopolymerization of styrene led to essentially no conversion after 48 h at 30 °C. However, the statistical copolymerization of 45% styrene with 55% nBA could be achieved using this low-temperature redox initiator at 30 °C using the same PNAEP67 precursor. In this case, 1H nuclear magnetic resonance studies indicated a significantly longer induction period (95 min) compared to either homopolymerization. Nevertheless, once the statistical copolymerization commenced, essentially full conversion of both comonomers could be achieved within 45 min. Differential scanning calorimetry analysis indicated that these statistical copolymers exhibited intermediate glass transition temperatures compared to the two respective homopolymers. The film formation behavior of selected diblock copolymer nanoparticles was briefly explored

Monodisperse macromolecules – A stepping stone to understanding industrial polymers

AbstractPolymers synthesized via anionic polymerization have proved important to our fundamental understanding of the processing, that is rheology and crystallisation, of bulk commodity polymers. The role of monodisperse hydrogenated polybutadienes as models for linear and branched polyethylene is examined. Systematic studies of the effects of long-chain branching, using well-defined “comb” materials have improved our understanding of how the number and length of branches affect the rheological properties and how these features impact on their crystallization behaviour. A combination of techniques including rheology, Small Angle X-ray Scattering (SAXS), and birefringence measurements have provided insight into role of linear long chains in the formation of oriented morphologies during the crystallization of hydrogenated polybutadiene blends of controlled polydispersity leading to the development of a quantitative model