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

The brain’s conversation with itself: neural substrates of dialogic inner speech

Inner speech has been implicated in important aspects of normal and atypical cognition, including the development of auditory hallucinations. Studies to date have focused on covert speech elicited by simple word or sentence repetition, while ignoring richer and arguably more psychologically significant varieties of inner speech. This study compared neural activation for inner speech involving conversations (‘dialogic inner speech’) with single-speaker scenarios (‘monologic inner speech’). Inner speech-related activation differences were then compared with activations relating to Theory-of-Mind (ToM) reasoning and visual perspective-taking in a conjunction design. Generation of dialogic (compared with monologic) scenarios was associated with a widespread bilateral network including left and right superior temporal gyri, precuneus, posterior cingulate and left inferior and medial frontal gyri. Activation associated with dialogic scenarios and ToM reasoning overlapped in areas of right posterior temporal cortex previously linked to mental state representation. Implications for understanding verbal cognition in typical and atypical populations are discussed

Modulating medial prefrontal cortex activity using real-time fMRI neurofeedback: Effects on reality monitoring performance and associated functional connectivity

Neuroimaging studies have found ‘reality monitoring’, our ability to distinguish internally generated experiences from those derived from the external world, to be associated with activity in the medial prefrontal cortex (mPFC) of the brain. Here we probe the functional underpinning of this ability using real-time fMRI neurofeedback to investigate the involvement of mPFC in recollection of the source of self-generated information. Thirty-nine healthy individuals underwent neurofeedback training in a between groups study receiving either Active feedback derived from the paracingulate region of the mPFC (21 subjects) or Sham feedback based on a similar level of randomised signal (18 subjects). Compared to those in the Sham group, participants receiving Active signal showed increased mPFC activity over the course of three real-time neurofeedback training runs undertaken in a single scanning session. Analysis of resting state functional connectivity associated with changes in reality monitoring accuracy following Active neurofeedback revealed increased connectivity between dorsolateral frontal regions of the fronto-parietal network (FPN) and the mPFC region of the default mode network (DMN), together with reduced connectivity within ventral regions of the FPN itself. However, only a trend effect was observed in the interaction of the recollection of the source of Imagined information compared with recognition memory between participants receiving Active and Sham neurofeedback, pre- and post- scanning. As such, these findings demonstrate that neurofeedback can be used to modulate mPFC activity and increase cooperation between the FPN and DMN, but the effects on reality monitoring performance are less clear

Obesity, Metabolic Syndrome, and Adipocytes

Obesity and metabolic syndromes are examples whereby excess energy consumption and energy flux disruptions are causative agents of increased fatness. Because other, as yet elucidated, cellular factors may be involved and because potential treatments of these metabolic problems involve systemic agents that are not adipose depot-specific in their actions, should we be thinking of adipose depot-specific (cellular) treatments for these problems? For sure, whether treating obesity or metabolic syndrome, the characteristics of all adipose depot-specific adipocytes and stromal vascular cells should be considered. The focus of this paper is to begin to align metabolic dysfunctions with specific characteristics of adipocytes

The sensuous secrets of shelter: how recollections of food stimulate Irish men's reconstructions of their early formative residential experiences in Leicester, Sheffield and Manchester

This paper examines the intersection between food, recollection and Irish migrants’ reconstructions of their housing pathways in the three English cities of Leicester (East Midlands), Sheffield (South Yorkshire) and Manchester (North). Previous studies have acknowledged more implicitly the role of memory in representing the Irish migrant experience in England. Here, we adopt a different stance. We explore the mnemonic power of food to encode, decode and recode Irish men’s reconstructions of their housing pathways in England when constructing and negotiating otherness. In doing so, we apply a ‘Proustian anthropological’ approach in framing the men’s representations of their formative residential experiences in the boarding houses of the three English cities during the 1950s and 1960s are examined. The extent to which food provided in the boarding houses was used as an instrument of discipline and control is examined. The relevance of food related acts of resistance, food insecurity and acts of hedonic meat-centric eating in constructing the men’s sociocultural identity are also explored

Successful outcome of six-level cervicothoracic corpectomy and circumferential reconstruction: case report and review of literature on multilevel cervicothoracic corpectomy

The authors report the successful outcome of a six-level corpectomy across the cervico-thoracic spine with circumferential reconstruction in a patient with extensive osteomyelitis of the cervical and upper thoracic spine. To the authors’ knowledge, this is the first report of a corpectomy extending across six levels of the cervico-thoracic spine. Clinical relevance: the authors recommend anterior cage and plate-assisted reconstruction and additional posterior instrumentation using modern spinal surgical techniques and implants

Errors in CGAP xProfiler and cDNA DGED: the importance of library parsing and gene selection algorithms

<p>Abstract</p> <p>Background</p> <p>The Cancer Genome Anatomy Project (CGAP) xProfiler and cDNA Digital Gene Expression Displayer (DGED) have been made available to the scientific community over a decade ago and since then were used widely to find genes which are differentially expressed between cancer and normal tissues. The tissue types are usually chosen according to the ontology hierarchy developed by NCBI. The xProfiler uses an internally available flat file database to determine the presence or absence of genes in the chosen libraries, while cDNA DGED uses the publicly available UniGene Expression and Gene relational databases to count the sequences found for each gene in the presented libraries.</p> <p>Results</p> <p>We discovered that the CGAP approach often includes libraries from dependent or irrelevant tissues (one third of libraries were incorrect on average, with some tissue searches no correct libraries being selected at all). We also discovered that the CGAP approach reported genes from outside the selected libraries and may omit genes found within the libraries. Other errors include the incorrect estimation of the significance values and inaccurate settings for the library size cut-off values. We advocated a revised approach to finding libraries associated with tissues. In doing so, libraries from dependent or irrelevant tissues do not get included in the final library pool. We also revised the method for determining the presence or absence of a gene by searching the UniGene relational database, revised calculation of statistical significance and sorted the library cut-off filter.</p> <p>Conclusion</p> <p>Our results justify re-evaluation of all previously reported results where NCBI CGAP expression data and tools were used.</p

End-group ionisation enables the use of poly(N-(2-methacryloyloxy)ethyl pyrrolidone) as an electrosteric stabiliser block for polymerisation-induced self-assembly in aqueous media

A series of near-monodisperse poly(N-2-(methacryloyloxy)ethyl pyrrolidone) (PNMEP) homopolymers was prepared via reversible addition-fragmentation chain transfer (RAFT) solution polymerisation of NMEP in ethanol at 70 °C using a carboxylic acid-functional RAFT agent. The mean degree of polymerisation (DP) was varied from 19 to 89 and acid titration indicated end-group pK a values of 5.07-5.44. Turbidimetry studies indicated that homopolymer cloud points were significantly higher at pH 7 (anionic carboxylate) than at pH 3 (neutral carboxylic acid). Moreover, this enhanced hydrophilic character enabled PNMEP to be used as a steric stabiliser for aqueous polymerisation-induced self-assembly (PISA) syntheses. Thus, a PNMEP 42 precursor was chain-extended via RAFT aqueous dispersion polymerisation of 2-hydroxypropyl methacrylate (HPMA) at 44 °C. A series of PNMEP 42 -PHPMA x diblock copolymers were synthesised using this protocol, with target PHPMA DPs of 150 to 400. High conversions were achieved and a linear evolution in M n with increasing PHPMA DP was observed. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies confirmed a spherical morphology in all cases. The nanoparticles flocculated either below pH 4.5 (owing to protonation) or on addition of 60 mM KCl (as a result of charge screening). Thus the anionic end-groups on the PNMEP stabiliser chains make an important contribution to the overall colloidal stability. Similarly, a PNMEP 53 macro-CTA was chain-extended via RAFT aqueous emulsion polymerisation of 2-ethoxyethyl methacrylate (EEMA) at 44 °C. Again, a neutral solution pH was critical for the synthesis of colloidally stable nanoparticles. High conversions were achieved as the target PEEMA DP was varied between 100 and 600 and a linear evolution in molecular weight with PEEMA DP was confirmed by chloroform GPC studies. DLS experiments indicated a monotonic increase in nanoparticle diameter with PEEMA DP and TEM studies confirmed a spherical morphology in each case. In summary, PNMEP can be used as a water-soluble steric stabiliser for aqueous PISA syntheses provided that it contains an anionic carboxylate end-group to enhance its hydrophilic character