Feasibility study of MgSO4 + zeolite based composite thermochemical energy stores charged by vacuum flat plate solar thermal collectors for seasonal thermal energy storage

A primary drawback of solar thermal technologies, especially in a domestic setting, is that collection of thermal energy occurs when solar irradiance is abundant and there is generally little requirement for heating. Thermochemical Energy Storage (TCES) offers a means of storing thermal energy interseasonally with little heat loss. A combination of a Solar Thermal Collector (STC) and TCES system will allow a variety of different heating applications, such as domestic space and hot water heating as well as low temperature industrial process heat applications to be met in a low carbon way. This paper describes and assesses the feasibility of two novel technologies currently under development at Loughborough University; i) an evacuated flat plate STC and ii) composite TCES materials, coupled together into a system designed to store and supply thermal energy on demand throughout the year. Experimental results of composite TCES materials along with predicted performance of STC's are used within a developed model to assess key metrics of conceptual TCES + STC systems feasibility, including; charging time, payback time, cost/kWh, energy savings and CO2 savings. This paper demonstrates the economic, energy and carbon savings potential of conceptual TCES + STC systems suitable for domestic use

miRNA-Mediated Regulation of Adult Hippocampal Neurogenesis; Implications for Epilepsy

Hippocampal neural stem/progenitor cells (NSPCs) proliferate and differentiate to generate new neurons across the life span of most mammals, including humans. This process takes place within a characteristic local microenvironment where NSPCs interact with a variety of other cell types and encounter systemic regulatory factors. Within this microenvironment, cell intrinsic gene expression programs are modulated by cell extrinsic signals through complex interactions, in many cases involving short non-coding RNA molecules, such as miRNAs. Here we review the regulation of gene expression in NSPCs by miRNAs and its possible implications for epilepsy, which has been linked to alterations in adult hippocampal neurogenesis

Proteomic analysis of 14-3-3 zeta binding proteins in the mouse hippocampus.

14-3-3 proteins are ubiquitous molecular chaperones with important roles in brain development and neuronal function. Altered expression of 14-3-3 proteins has been reported in several neurologic and neurodegenerative disorders and identifying 14-3-3 binding proteins may provide important insights into the physiologic and pathophysiologic roles of these proteins. Particular interest has emerged on 14-3-3 zeta (ζ) in the setting of neuronal injury because reducing 14-3-3ζ levels triggers an endoplasmic reticulum stress-like response in neurons and increases vulnerability to excitotoxicity. Here we examined the subcellular distribution of 14-3-3ζ in the mouse hippocampus. We then used recombinant His-tagged 14-3-3ζ to pull-down interacting proteins from the mouse hippocampus followed by identification by liquid chromatography-mass spectrometry. 14-3-3ζ protein was present in the cytoplasm, microsomal compartment, nucleus and mitochondrial fractions of the mouse hippocampus. Recombinant 14-3-3ζ eluted 13 known 14-3-3 binding partners, including three other 14-3-3 isoforms, and 16 other proteins which have not previously been reported to bind 14-3-3ζ. The present study identifies potentially novel 14-3-3ζ binding proteins and contributes to defining the 14-3-3ζ interactome in the mouse brain

The Anthropomorphic Application of Gender Stereotypes to Horses

Gender stereotypes shape human social interaction, often to the detriment of women and those who do not comply with normative expectations of gender. So far, little research has assessed the extent to which people apply gender stereotypes to animals, and the implications this may have for individuals and groups, particularly female animals. The current study investigated survey respondents’ preference for horses to perform in different sport and leisure practices, based solely on ideas about the sex of the animal. An anonymous online survey explored the preferences of riders for mares, geldings and stallions for dressage, show-jumping and trail-riding, and reasons for their choice. A total of 1032 responses were received. Geldings were the preferred choice, being perceived as safe and reliable, followed by stallions who were valued for their supposed power, presence and good looks. Overall, mares were the least popular choice, and were discussed in ambivalent terms reflecting broad gender stereotypes which depict females as moody, flighty and unpredictable. Respondents appeared to draw on gender stereotypes to make judgements about horses and justify their choices. The anthropomorphic application of gender stereotypes to animals may have negative consequences for female animals, shaping human-animal interactions and expectations

Transgenic overexpression of 14-3-3 zeta protects hippocampus against endoplasmic reticulum stress and status epilepticus in vivo.

14-3-3 proteins are ubiquitous molecular chaperones that are abundantly expressed in the brain where they regulate cell functions including metabolism, the cell cycle and apoptosis. Brain levels of several 14-3-3 isoforms are altered in diseases of the nervous system, including epilepsy. The 14-3-3 zeta (ζ) isoform has been linked to endoplasmic reticulum (ER) function in neurons, with reduced levels provoking ER stress and increasing vulnerability to excitotoxic injury. Here we report that transgenic overexpression of 14-3-3ζ in mice results in selective changes to the unfolded protein response pathway in the hippocampus, including down-regulation of glucose-regulated proteins 78 and 94, activating transcription factors 4 and 6, and Xbp1 splicing. No differences were found between wild-type mice and transgenic mice for levels of other 14-3-3 isoforms or various other 14-3-3 binding proteins. 14-3-3ζ overexpressing mice were potently protected against cell death caused by intracerebroventricular injection of the ER stressor tunicamycin. 14-3-3ζ overexpressing mice were also potently protected against neuronal death caused by prolonged seizures. These studies demonstrate that increased 14-3-3ζ levels protect against ER stress and seizure-damage despite down-regulation of the unfolded protein response. Delivery of 14-3-3ζ may protect against pathologic changes resulting from prolonged or repeated seizures or where injuries provoke ER stress

Transcriptional response of polycomb group genes to status epilepticus in mice is modified by prior exposure to epileptic preconditioning.

Exposure of the brain to brief, non-harmful seizures can activate protective mechanisms that temporarily generate a damage-refractory state. This process, termed epileptic tolerance, is associated with large-scale down-regulation of gene expression. Polycomb group (PcG) proteins are master controllers of gene silencing during development that are re-activated by injury to the brain. Here, we explored the transcriptional response of genes associated with polycomb repressive complex (PRC) 1 (Ring1A, Ring1B, and Bmi1) and PRC2 (Ezh1, Ezh2, and Suz12), as well as additional transcriptional regulators Sirt1, Yy1, and Yy2, in a mouse model of status epilepticus (SE). Findings were contrasted to changes after SE in mice previously given brief seizures to evoke tolerance. Real-time quantitative PCR showed SE prompted an early (1 h) increase in expression of several genes in PRC1 and PRC2 in the hippocampus, followed by down-regulation of many of the same genes at later times points (4, 8, and 24 h). Spatio-temporal differences were found among PRC2 genes in epileptic tolerance, including increased expression of Ezh2, Suz12, and Yy2 relative to the normal injury response to SE. In contrast, PRC1 complex genes including Ring 1B and Bmi1 displayed differential down-regulation in epileptic tolerance. The present study characterizes PcG gene expression following SE and shows prior seizure exposure produces select changes to PRC1 and PRC2 composition that may influence differential gene expression in epileptic tolerance

Interventions to improve the uptake of breast, cervical and bowel cancer screening in South Asian women living in high income countries

Objectives: The aim of this review was to identify the cultural, social, structural and behavioural factors that influence asymptomatic breast and cervical cancer screening attendance in South Asian populations, in order to improve uptake and propose priorities for further research. Design: A systematic review of the literature for inductive, comparative, prospective and intervention studies. We searched the following databases: MEDLINE/In-Process; Web of Science; EMBASE; SCOPUS; CENTRAL; CDSR; CINAHL; PsycINFO and PsycARTICLES from database inception to 23 January 2018. The review included studies on the cultural, social, structural and behavioural factors that influence asymptomatic breast and cervical cancer screening attendance and cervical smear testing (Papanicolaou test) in South Asian populations and those published in the English language. The Framework Analytic method was used and themes were drawn out following the Thematic Analysis method. Settings: Asymptomatic breast or cervical screening Participants: South Asian women, including Bangladeshi, Indian, Pakistani, Sri Lankan, Bhutanese, Maldivian and Nepali populations. Results: 51 included studies were published between 1991 and 2018. Sample sizes ranged from 25 to 38,733 and participants had a mean age of 18 to 83 years. Our review showed that South Asian women generally had lower screening rates than host country women. South Asian women had poorer knowledge of cancer and cancer prevention and experienced more barriers to screening. Cultural practices and assumptions influenced understandings of cancer and prevention, emphasising the importance of host country cultures and healthcare systems. Conclusions: High quality research on screening attendance is required using prospective designs, where objectively-validated attendance is predicted from cultural understandings, beliefs, norms and practices; thus informing policy on targeting relevant public health messages to the South Asian communities about screening for cancer

Mutation of Semaphorin-6A Disrupts Limbic and Cortical Connectivity and Models Neurodevelopmental Psychopathology

Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism

Spatiotemporal progression of ubiquitin-proteasome system inhibition after status epilepticus suggests protective adaptation against hippocampal injury.

BACKGROUND: The ubiquitin-proteasome-system (UPS) is the major intracellular pathway leading to the degradation of unwanted and/or misfolded soluble proteins. This includes proteins regulating cellular survival, synaptic plasticity and neurotransmitter signaling; processes controlling excitability thresholds that are altered by epileptogenic insults. Dysfunction of the UPS has been reported to occur in a brain region- and cell-specific manner and contribute to disease progression in acute and chronic brain diseases. Prolonged seizures, status epilepticus, may alter UPS function but there has been no systematic attempt to map when and where this occurs in vivo or to determine the consequences of proteasome inhibition on seizure-induced brain injury. METHOD: To determine whether seizures lead to an impairment of the UPS, we used a mouse model of status epilepticus whereby seizures are triggered by an intra-amygdala injection of kainic acid. Status epilepticus in this model causes cell death in selected brain areas, in particular the ipsilateral CA3 subfield of the hippocampus, and the development of epilepsy after a short latent period. To monitor seizure-induced dysfunction of the UPS we used a UPS inhibition reporter mouse expressing the ubiquitin fusion degradation substrate ubiquitin(G76V)-green fluorescent protein. Treatment with the specific proteasome inhibitor epoxomicin was used to establish the impact of proteasome inhibition on seizure-induced pathology. RESULTS AND CONCLUSIONS: Our studies show that status epilepticus induced by intra-amygdala kainic acid causes select spatio-temporal UPS inhibition which is most evident in damage-resistant regions of the hippocampus, including CA1 pyramidal and dentate granule neurons then appears later in astrocytes. In support of this exerting a beneficial effect, injection of mice with the proteasome inhibitor epoxomicin protected the normally vulnerable hippocampal CA3 subfield from seizure-induced neuronal death in the model. These studies reveal brain region- and cell-specific UPS impairment occurs after seizures and suggest UPS inhibition can protect against seizure-induced brain damage. Identifying networks or pathways regulated through the proteasome after seizures may yield novel target genes for the treatment of seizure-induced cell death and possibly epilepsy