Epigenetic control of the vasopressin promoter explains physiological ability to regulate vasopressin transcription in dehydration and salt loading states in the rat

The synthesis of arginine vasopressin (AVP) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus is sensitive to increased plasma osmolality and a decreased blood volume, and thus is robustly increased by both dehydration (increased plasma osmolality and decreased blood volume) and salt loading (increased plasma osmolality). Both stimuli result in functional remodelling of the SON and PVN, a process referred to as functional‐related plasticity. Such plastic changes in the brain have recently been associated with altered patterns of DNA methylation at CpG (cytosine‐phosphate‐guanine) residues, a process considered to be important for the regulation of gene transcription. In this regard, the proximal Avp promoter contains a number of CpG sites and is recognised as one of four CpG islands for the Avp gene, suggesting that methylation may be regulating Avp transcription. In the present study, we show that, in an immortalised hypothalamic cell line 4B, the proximal Avp promoter is highly methylated, and treatment of these cells with the DNA methyltransferase inhibitor 5‐Aza‐2′‐deoxycytidine to demethylate DNA dramatically increases basal and stimulated Avp biosynthesis. We report no changes in the expression of DNA methyltransferases, Dnmt1 and Dnmt3a, whereas there is decreased expression of the demethylating enzyme ten‐eleven‐translocation 2, Tet2, in the SON by dehydration and salt loading. We found higher methylation of the SON Avp promoter in dehydrated but not salt‐loaded rats. By analysis of individual CpG sites, we observed hypomethylation, hypermethylation and no change in methylation of specific CpGs in the SON Avp promoter of the dehydrated rat. Using reporter gene assays, we show that mutation of individual CpGs can result in altered Avp promoter activity. We propose that methylation of the SON Avp promoter is necessary to co‐ordinate the duel inputs of increased plasma osmolality and decreased blood volume on Avp transcription in the chronically dehydrated rat

Thermal modeling of lithium ion batteries for temperature rise predictions in hybrid vehicle application

In order to develop a hybrid vehicle with lithium ion battery packs, it is necessary to understand the thermal behaviour of the lithium ion batteries used. This paper focuses on predicting the temperature rise of lithium ion batteries during a drive cycle in hybrid two wheeler applications. To predict the rise in temperature, a model is developed in Simulink, parameterized using the empirical parameters. The model is based on the Joule heating effect and heat capacity equation while considering the variation of internal resistance with respect to ambient temperature of operation, state of charge and C rate of operation. The internal resistance is measured by parameter evaluation testing through the pulse power characterisation method. To validate the Simulink model, the lithium ion batteries are tested on standard drive cycles and constant current discharges, and the rise in temperature is measured. The accuracy of the Simulink model was found to be ± 2.2°C, which is acceptable for this study and comparable to the other available models in the literature

Pigment stability studies in selected pigment-producing microbes from New Zealand environment

The industrial production of natural food colourants is already well-established and expanding. However, the range of natural colour-shades is still limited compared to synthetic dyes. Besides, the use of plant extracts is known to be expensive and uncompetitive to synthetic dyes due to their high production costs. Consequently, microorganisms are becoming a more popular alternative source for natural food grade pigments. Development of microbial food grade pigments are likely to cut down the high production cost of natural colours, thus leading to a cheaper source of natural food colourants among the modern consumers. Preceding commercialization, pigment stability and toxicity assessment are required in order to determine their suitability to the food industry. We, therefore, have screened 286 pigment-producing microbial strains isolated from New Zealand environment. Based on water solubility and colour-shades of interest, 41 pigments have been short-listed for pigment stability tests towards different pHs, temperatures and light. To date, our current results showed that 81% of the yellow-to-reddish water-soluble pigments and the red SVB-B50 water-insoluble pigment were stable at all ranges of temperature i.e. -20oC, 4oC, 60oC, 100oC and microwave heat. Light and pH stability tests are being carried out. Further to this study, metabolomics tools will be incorporated to elucidate the metabolic pathway for biosynthesis of a selected microbial pigment with most potential for industrial application, and metabolic engineering strategies will be determined aiming for improvement of the pigment production yields during fermentation

A study into different cell-level cooling strategies for cylindrical lithium-ion cells in automotive applications

Previous research has identified that the ageing rate and performance of lithium-ion cells is negatively influenced by unfavourable cell thermal conditions, specifically, high ambient temperatures and large in-cell temperature gradients. In this paper, the effectiveness of different cell cooling strategies on reducing the in-cell temperature gradient within cylindrical cells is analysed through the development of a 2-D transient bulk layer thermal model displaying anisotropic thermal conductivity. The model is validated against experimental temperature measurements in which the peak error of the simulation was found to be 2% and 5% for the experimental test drive cycle and constant 1C discharge respectively. Results indicate that radial cooling with air or singular tab cooling with liquid may be inadequate in limiting cell temperature gradients to below 5 ℃ for HEV type 32113 cells when subject to 4 loops of the US06 drive cycle

Transcription factor CREB3L1 mediates cAMP and glucocorticoid regulation of arginine vasopressin gene transcription in the rat hypothalamus

BACKGROUND: Arginine vasopressin (AVP), a neuropeptide hormone that functions in the regulation of water homeostasis by controlling water re-absorption at kidneys, is synthesised in supraoptic nucleus and paraventricular nucleus of the hypothalamus. An increase in plasma osmolality stimulates secretion of AVP to blood circulation and induces AVP synthesis in these nuclei. Although studies on mechanism of AVP transcriptional regulation in hypothalamus proposed that cAMP and glucocorticoids positively and negatively regulate Avp expression, respectively, the molecular mechanisms have remained elusive. Recently, we identified CREB3L1 (cAMP-responsive element binding protein 3 like 1) as a putative transcription factor of Avp transcription in the rat hypothalamus. However the mechanism of how CREB3L1 is regulated in response of hyperosmotic stress in the neurons of hypothalamus has never been reported. This study aims to investigate effect of previously reported regulators (cAMP and glucocorticoid) of Avp transcription on transcription factor CREB3L1 in order to establish a molecular explanation for cAMP and glucocorticoids effect on AVP expression. RESULTS: The effect of cAMP and glucocorticoid treatment on Creb3l1 was investigated in both AtT20 cells and hypothalamic organotypic cultures. The expression of Creb3l1 was increased in both mRNA and protein level by treatment with forskolin, which raises intracellular cAMP levels. Activation of cAMP by forskolin also increased Avp promoter activity in AtT20 cells and this effect was blunted by shRNA mediated silencing of Creb3l1. The forskolin induced increase in Creb3l1 expression was diminished by combined treatment with dexamethasone, and, in vivo, intraperitoneal dexamethasone injection blunted the increase in Creb3l1 and Avp expression induced by hyperosmotic stress. CONCLUSION: Here we shows that cAMP and glucocorticoid positively and negatively regulate Creb3l1 expression in the rat hypothalamus, respectively, and regulation of cAMP on AVP expression is mediated through CREB3L1. This data provides the connection between CREB3L1, a newly identified transcription factor of AVP expression, with the previously proposed mechanism of Avp transcription which extends our understanding in transcription regulation of Avp in the hypothalamus

Regulation of cAMP Responsive Element Binding Protein 3-Like 1 (Creb3l1) Expression by Orphan Nuclear Receptor Nr4a1

Cyclic AMP (cAMP) inducible transcription factor cAMP responsive element binding protein 3 like 1 (Creb3l1) is strongly activated in the hypothalamus in response to hyperosmotic cues such as dehydration (DH). We have recently shown that Creb3l1 expression is upregulated by cAMP pathways in vitro, however the exact mechanisms are not known. Here we show that increasing Creb3l1 transcription by raising cAMP levels in mouse pituitary AtT20 cells automatically initiates cleavage of Creb3l1, leading to a greater abundance of the transcriptionally active N-terminal portion. Inhibiting protein synthesis indicated that de novo protein synthesis of an intermediary transcription factor was required for Creb3l1 induction. Strategic mining of our microarray data from dehydrated rodent hypothalamus revealed four candidates, reduced to two by analysis of acute hyperosmotic-induced transcriptional activation profiles in the hypothalamus, and one, orphan nuclear receptor Nr4a1, by direct shRNA mediated silencing in AtT20 cells. We show that activation of Creb3l1 transcription by Nr4a1 involves interaction with a single NBRE site in the promoter region. The ability to activate Creb3l1 transcription by this pathway in vitro is dictated by the level of methylation of a CpG island within the proximal promoter/5′UTR of this gene. We thus identify a novel cAMP-Nr4a1-Creb3l1 transcriptional pathway in AtT20 cells and also, our evidence would suggest, in the hypothalamus

Great Canadian Lagerstätten 1. Early Eocene Lagerstätten of the Okanagan Highlands (British Columbia and Washington State)

The Early Eocene Okanagan High lands series of lacustrine shale and coal deposits, in far western North Ameri ca, constitutes a significant group of fossil sites with exceptional preserva tion of a diverse suite of organisms (Lagerstätten). With contemporaneous basins arrayed across about 1000 kilo metres of southern British Columbia and northern Washington, these sites offer a unique opportunity to examine the paleoecology of terrestrial commu nities spanning a temperate, low-sea sonality landscape in a montane setting during a time of generally warm tem peratures across the globe. The Okana gan Highlands sites provide an unpar alleled comparative framework within which to examine this major turning point in terrestrial community develop ment during the emergence of their broad modern character.La série de dépôts lacustres de schiste et de charbon du début de l’Éocène des hautes terres d’Okanagan, aux con fins de l’ouest de l’Amérique du Nord, constituent un groupe important de sites fossiles particulièrement bien con servés de suites d’organismes diverses (Lagerstätten). De nos jours, ces sites forment en une bande d’environ 1 000 kilomètres, depuis le sud de la Colom bie-Britannique jusqu’au nord de l’État de Washington. Dans le contexte de réchauffement climatique, c’est l’occa sion ou jamais d’étudier la paléoécolo gie de communautés terrestres dans des conditions climatiques modérées dans un paysage de montagne à faible saisonnalité. Les sites des hautes terres d’Okanagan représentent un cadre de comparaison sans pareil permettant d’étudier les effets de ce tournant majeur sur le développement des prin cipales caractéristiques modernes de la communauté terrestre

Understanding the future impacts of electric vehicles — an analysis of multiple factors that influence the market

The electric vehicle market is an increasingly important aspect of the automotive industry. However, as a relatively new technology, several issues remain present within the industry. An analysis is utilised to examine these issues, along with how they affect the industry and how they can be tackled. Several key issues that affect the electric vehicle market, as well as how efforts to address these issues influence the market, are identified. The analysis also includes the examination of ethical issues, with the issues that arise from the production of raw materials for electric vehicles. The analysis and examination of ethical issues display a wide range of problems in the industry. However, it did highlight the efforts being made to lessen the effect of these problems by various groups, such as regulation by EU and US governing bodies on the materials mined. From this analysis, this paper identifies that many of the other factors examined are directly or indirectly influenced by political and economic factors, also examined in this review. This highlights the impact that governing bodies and businesses have on a vast number of issues that are present within the market and how they can resolve the harmful factors examined

Effectiveness of structured patient-clinician communication with a solution focused approach (DIALOG+) in community treatment of patients with psychosis - a cluster randomised controlled trial

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