Characterisation of the maternal response to chronic phase shifts during gestation in the rat: implications for fetal metabolic programming

Disrupting maternal circadian rhythms through exposure to chronic phase shifts of the photoperiod has lifelong consequences for the metabolic homeostasis of the fetus, such that offspring develop increased adiposity, hyperinsulinaemia and poor glucose and insulin tolerance. In an attempt to determine the mechanisms by which these poor metabolic outcomes arise, we investigated the impact of chronic phase shifts (CPS) on maternal and fetal hormonal, metabolic and circadian rhythms. We assessed weight gain and food consumption of dams exposed to either CPS or control lighting conditions throughout gestation. At day 20, dams were assessed for plasma hormone and metabolite concentrations and glucose and insulin tolerance. Additionally, the expression of a range of circadian and metabolic genes was assessed in maternal, placental and fetal tissue. Control and CPS dams consumed the same amount of food, yet CPS dams gained 70% less weight during the first week of gestation. At day 20, CPS dams had reduced retroperitoneal fat pad weight (−15%), and time-of-day dependent decreases in liver weight, whereas fetal and placental weight was not affected. Melatonin secretion was not altered, yet the timing of corticosterone, leptin, glucose, insulin, free fatty acids, triglycerides and cholesterol concentrations were profoundly disrupted. The expression of gluconeogenic and circadian clock genes in maternal and fetal liver became either arrhythmic or were in antiphase to the controls. These results demonstrate that disruptions of the photoperiod can severely disrupt normal circadian profiles of plasma hormones and metabolites, as well as gene expression in maternal and fetal tissues. Disruptions in the timing of food consumption and the downstream metabolic processes required to utilise that food, may lead to reduced efficiency of growth such that maternal weight gain is reduced during early embryonic development. It is these perturbations that may contribute to the programming of poor metabolic homeostasis in the offspring.Tamara J. Varcoe, Michael J. Boden, Athena Voultsios, Mark D. Salkeld, Leewen Rattanatray, David J. Kennawa

Conserved Expression of the Glutamate NMDA Receptor 1 Subunit Splice Variants during the Development of the Siberian Hamster Suprachiasmatic Nucleus

Glutamate neurotransmission and the N-methyl-D-aspartate receptor (NMDAR) are central to photic signaling to the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). NMDARs also play important roles in brain development including visual input circuits. The functional NMDAR is comprised of multiple subunits, but each requiring the NR1 subunit for normal activity. The NR1 can be alternatively spliced to produce isoforms that confer different functional properties on the NMDAR. The SCN undergoes extensive developmental changes during postnatal life, including synaptogenesis and acquisition of photic signaling. These changes are especially important in the highly photoperiodic Siberian hamster, in which development of sensitivity to photic cues within the SCN could impact early physiological programming. In this study we examined the expression of NR1 isoforms in the hamster at different developmental ages. Gene expression in the forebrain was quantified by in situ hybridization using oligonucleotide probes specific to alternatively spliced regions of the NR1 heteronuclear mRNA, including examination of anterior hypothalamus, piriform cortex, caudate-putamen, thalamus and hippocampus. Gene expression analysis within the SCN revealed the absence of the N1 cassette, the presence of the C2 cassette alone and the combined absence of C1 and C2 cassettes, indicating that the dominant splice variants are NR1-2a and NR1-4a. Whilst we observe changes at different developmental ages in levels of NR1 isoform probe hybridization in various forebrain structures, we find no significant changes within the SCN. This suggests that a switch in NR1 isoform does not underlie or is not produced by developmental changes within the hamster SCN. Consistency of the NR1 isoforms would ensure that the response of the SCN cells to photic signals remains stable throughout life, an important aspect of the function of the SCN as a responder to environmental changes in quality/quantity of light over the circadian day and annual cycle

Importance of balancing membrane and electrode water in anion exchange membrane fuel cells

Anion exchange membrane fuel cells (AEMFCs) offer several potential advantages over proton exchange membrane fuel cells (PEMFCs), most notably to overcome the cost barrier that has slowed the growth and large scale implementation of fuel cells for transportation. However, limitations in performance have held back AEMFCs, specifically in the areas of stability, carbonation, and maximum achievable current and power densities. In order for AEMFCs to contend with PEMFCs for market viability, it is necessary to realize a competitive cell performance. This work demonstrates a new benchmark for a H2/O2 AEMFC with a peak power density of 1.4 W cm−2 at 60 °C. This was accomplished by taking a more precise look at balancing necessary membrane hydration while preventing electrode flooding, which somewhat surprisingly can occur both at the anode and the cathode. Specifically, radiation-grafted ETFE-based anion exchange membranes and anion exchange ionomer powder, functionalized with benchmark benzyltrimethylammonium groups, were utilized to examine the effects of the following parameters on AEMFC performance: feed gas flow rate, the use of hydrophobic vs. hydrophilic gas diffusion layers, and gas feed dew points

Carbonate Dynamics and Opportunities With Low Temperature, Anion Exchange Membrane-Based Electrochemical Carbon Dioxide Separators

Fossil fuel power plants are responsible for a significant portion of anthropogenic atmospheric carbon dioxide (CO2) and due to concerns over global climate change, finding solutions that significantly reduce emissions at their source has become a vital concern. When oxygen (O2) is reduced along with CO2 at the cathode of an anion exchange membrane (AEM) electrochemical cell, carbonate and bicarbonate are formed which are transported through electrolyte by migration from the cathode to the anode where they are oxidized back to CO2 and O2. This behavior makes AEM-based devices scientifically interesting CO2 separation devices or “electrochemical CO2 pumps.” Electrochemical CO2 separation is a promising alternative to state-of-the-art solvent-based methods because the cells operate at low temperatures and scale with surface area, not volume, suggesting that industrial electrochemical systems could be more compact than amine sorption technologies. In this work, we investigate the impact of the CO2 separator cell potential on the CO2 flux, carbonate transport mechanism and process costs. The applied electrical current and CO2 flux showed a strong correlation that was both stable and reversible. The dominant anion transport pathway, carbonate vs. bicarbonate, undergoes a shift from carbonate to mixed carbonate/bicarbonate with increased potential. A preliminary techno-economic analysis shows that despite the limitations of present cells, there is a clear pathway to meet the US DOE 2025 and 2035 targets for power plant retrofit CO2 capture systems through materials and systems-level advances

Carbonate Dynamics and Opportunities With Low Temperature, Anion Exchange Membrane-Based Electrochemical Carbon Dioxide Separators

Fossil fuel power plants are responsible for a significant portion of anthropogenic atmospheric carbon dioxide (CO2) and due to concerns over global climate change, finding solutions that significantly reduce emissions at their source has become a vital concern. When oxygen (O2) is reduced along with CO2 at the cathode of an anion exchange membrane (AEM) electrochemical cell, carbonate and bicarbonate are formed which are transported through electrolyte by migration from the cathode to the anode where they are oxidized back to CO2 and O2. This behavior makes AEM-based devices scientifically interesting CO2 separation devices or “electrochemical CO2 pumps.” Electrochemical CO2 separation is a promising alternative to state-of-the-art solvent-based methods because the cells operate at low temperatures and scale with surface area, not volume, suggesting that industrial electrochemical systems could be more compact than amine sorption technologies. In this work, we investigate the impact of the CO2 separator cell potential on the CO2 flux, carbonate transport mechanism and process costs. The applied electrical current and CO2 flux showed a strong correlation that was both stable and reversible. The dominant anion transport pathway, carbonate vs. bicarbonate, undergoes a shift from carbonate to mixed carbonate/bicarbonate with increased potential. A preliminary techno-economic analysis shows that despite the limitations of present cells, there is a clear pathway to meet the US DOE 2025 and 2035 targets for power plant retrofit CO2 capture systems through materials and systems-level advances

Sleep disturbances in women with polycystic ovary syndrome: prevalence, pathophysiology, impact and management strategies

Renae C Fernandez,1–3 Vivienne M Moore,1,3,4 Emer M Van Ryswyk,5 Tamara J Varcoe,1,2 Raymond J Rodgers,1,2 Wendy A March,1,3 Lisa J Moran,1,6 Jodie C Avery,1,2 R Doug McEvoy,5,7 Michael J Davies1,2 1The University of Adelaide, Robinson Research Institute, Adelaide, SA, Australia; 2The University of Adelaide, Adelaide Medical School, Adelaide, SA, Australia; 3The University of Adelaide, School of Public Health, Adelaide, SA, Australia; 4The University of Adelaide, Fay Gale Centre for Research on Gender, Adelaide, SA, Australia; 5Adelaide Institute for Sleep Health, Flinders Centre for Research Excellence, Flinders University of South Australia, Bedford Park, SA, Australia; 6Monash Centre for Health Research Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia; 7Adelaide Sleep Health, Southern Adelaide Local Health Network, Repatriation General Hospital, Daw Park, SA, Australia Abstract: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting the reproductive, metabolic and psychological health of women. Clinic-based studies indicate that sleep disturbances and disorders including obstructive sleep apnea and excessive daytime sleepiness occur more frequently among women with PCOS compared to comparison groups without the syndrome. Evidence from the few available population-based studies is supportive. Women with PCOS tend to be overweight/obese, but this only partly accounts for their sleep problems as associations are generally upheld after adjustment for body mass index; sleep problems also occur in women with PCOS of normal weight. There are several, possibly bidirectional, pathways through which PCOS is associated with sleep disturbances. The pathophysiology of PCOS involves hyperandrogenemia, a form of insulin resistance unique to affected women, and possible changes in cortisol and melatonin secretion, arguably reflecting altered hypothalamic–pituitary–adrenal function. Psychological and behavioral pathways are also likely to play a role, as anxiety and depression, smoking, alcohol use and lack of physical activity are also common among women with PCOS, partly in response to the distressing symptoms they experience. The specific impact of sleep disturbances on the health of women with PCOS is not yet clear; however, both PCOS and sleep disturbances are associated with deterioration in cardiometabolic health in the longer term and increased risk of type 2 diabetes. Both immediate quality of life and longer-term health of women with PCOS are likely to benefit from diagnosis and management of sleep disorders as part of interdisciplinary health care. Keywords: polycystic ovary syndrome, sleep, sleep disturbance, hypothalamic-pituitary-adrenal, cardiometabolic healt

MDMA induces Per1, Per2 and c-fos gene expression in rat suprachiasmatic nuclei

RATIONALE: ±3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a psychoactive drug that has marked effects on the serotonergic system. Serotonergic agonists are known to interact with the circadian pacemaker located in the suprachiasmatic nuclei (SCN). OBJECTIVES: Given changes reported in the behavioral activity rhythm followingMDMAtreatment, the effects ofMDMAon core clock gene (Per1, Per2) and c-fos expression were evaluated. METHODS: Male Long–Evans rats (n=72) were injected once with MDMA (5 mg/kg i.p.) or saline either at the middle of their ‘rest’ phase (Zeitgeber Time: ZT6) or the middle of their ‘active’ phase (Zeitgeber Time: ZT16) and killed at 30, 60, or 120 min posttreatment for gene expression analysis in the SCN using PCR. Behavioral rhythms of a separate group of rats (n=20) were measured following treatment at ZT16 while they were held in constant darkness for 10 days posttreatment. RESULTS: At ZT6, c-fos mRNA was significantly induced 120 min post-MDMA treatment but there were no significant changes in Per1 or Per2 mRNA expression. At ZT16, there were significant inductions of c-fos mRNA (30 and 60 min) and Per1 and Per2 mRNA (both 60 min) post-MDMA treatment. However, no differences in behavioral activity patterns were noted following MDMA treatment at ZT16. CONCLUSIONS: These data provide evidence that MDMA has time of day dependent actions on SCN functioning, as evident from its induction of core clock genes that are important for generating and maintaining circadian rhythmicity.Rowan P. Ogeil, David J. Kennaway, Mark D. Salkeld, Shantha M.W. Rajaratnam and Jillian H. Broadbea