The duodenum secretes HCO3− as part of a multi‐layered series of defence mechanisms against damage from luminal acid. In the 1980s, an alkaline surface layer was measured over the mucosa which ...correlated with the rate of HCO3− secretion. As all biological processes are regulated, we investigated how the alkaline pH of the surface layer was maintained. As the ecto‐phosphorylase alkaline phosphatase (AP) is highly expressed in the duodenal brush border, we hypothesized that its extreme alkaline pH optimum (∼pH 8–9) combined with its ability to hydrolyse regulatory purines such as ATP was part of an ecto‐purinergic signalling system, consisting also of brush border P2Y receptors and cystic fibrosis transmembrane regulator‐mediated HCO3− secretion. Extracellular ATP increases the rate of HCO3− secretion through this purinergic system. At high surface pH (pHs), AP activity is increased, which then increases the rate of ATP hydrolysis, decreasing surface ATP concentration (ATPs), with a resultant decrease in the rate of HCO3− secretion, which subsequently decreases pHs. This feedback loop is thus hypothesized to regulate pHs over the duodenal mucosa, and in several other HCO3− secretory organs. As AP activity is directly related to pHs, and as AP hydrolyses ATP, ATPs and pHs are co‐regulated. As many essential tissue functions such as ciliary motility and lipid uptake are dependent on ATPs, dysregulation of pHs and ATPs may help explain the tissue dysfunction characteristic of diseases such as cystic fibrosis.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
The duodenum serves as a buffer zone between the stomach and the jejunum. Over a length of only 25 cm, large volumes of strong acid secreted by the stomach must be converted to the ...neutral–alkaline chyme of the hindgut lumen, generating large volumes of CO2.
The duodenal mucosa consists of epithelial cells connected by low‐resistance tight junctions, forming a leaky epithelial barrier. Despite this permeability, the epithelial cells, under intense stress from luminal mineral acid and highly elevated Pco2, maintain normal functioning.
Bicarbonate ion uniquely protects the duodenal epithelial cells from acid‐related injury. The specific protective mechanisms likely involve luminal bicarbonate secretion, intracellular pH buffering and interstitial buffering. Furthermore, the duodenum plays an active role in foregut acid–base homeostasis, absorbing large amounts of H+ and CO2.
We have studied mucosal protection and acid–base balance using live‐animal fluorescence ratio microimaging and by performing H+ and CO2 balance studies on duodenal perfusates. On the basis of these data, we have formulated novel hypotheses with regard to mucosal protection.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Acid in the oesophageal lumen is often sensed as heartburn. It was hypothesised that luminal CO(2), a permeant gas, rather than H(+), permeates through the epithelium, and is converted to H(+), ...producing an afferent neural signal by activating chemosensors.
The rat lower oesophageal mucosa was superfused with pH 7.0 buffer, and pH 1.0 or pH 6.4 high CO(2) (P(CO2) = 260 Torr) solutions with or without the cell-permeant carbonic anhydrase (CA) inhibitor methazolamide (MTZ, 1 mM), the cell-impermeant CA inhibitor benzolamide (BNZ, 0.1 mM), the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ, 0.5 mM) or the acid-sensing ion channel (ASIC) inhibitor amiloride (0.1 mM). Interstitial pH (pH(int)) was measured with 5',6'-carboxyfluorescein (5 mg/kg intravenously) loaded into the interstitial space, and blood flow was measured with laser-Doppler.
Perfusion of a high CO(2) solution induced hyperaemia without changing pH(int), mimicking the effect of pH 1.0 perfusion. Perfused MTZ, BNZ, CPZ and amiloride all inhibited CO(2)-induced hyperaemia. CA XIV was expressed in the prickle cells, with CA XII in the basal cells. TRPV1 was expressed in the stratum granulosum and in the muscularis mucosa, whereas all ASICs were expressed in the prickle cells, with ASIC3 additionally in the muscularis mucosa.
The response to CO(2) perfusion suggests that CO(2) diffuses through the stratum epithelium, interacting with TRPV1 and ASICs in the epithelium or in the submucosa. Inhibition of the hyperaemic response to luminal CO(2) by CA, TRPV1 and ASIC inhibitors implicates CA and these chemosensors in transduction of the luminal acid signal. Transepithelial CO(2) permeation may explain how luminal H(+) equivalents can rapidly be transduced into hyperaemia, and the sensation of heartburn.
Meal ingestion is followed by release of numerous hormones from enteroendocrine cells interspersed among the epithelial cells lining the intestine. Recently, the de-orphanization of G proteincoupled ...receptor (GPCR)-type nutrient receptors, expressed on the apical membranes of enteroendocrine cells, has suggested a plausible mechanism whereby luminal nutrients trigger the release of gut hormones. Activation of nutrient receptors triggers intracellular signaling mechanisms that promote exocytosis of hormone-containing granules into the submucosal space. Hormones released by foregut enteroendocrine cells include the glucagon-like peptides (GLP) affecting glycemic control (GLP-1) and releasing proproliferative, hypertrophy-inducing growth factors (GLP-2). The foregut mucosa, being exposed to pulses of concentrated HCl, is protected by a system of defense mechanisms, which includes epithelial bicarbonate and mucus secretion and augmentation of mucosal blood flow. We have reported that luminal co-perfusion of AA with nucleotides in anesthetized rats releases GLP-2 into the portal vein, associated with increased bicarbonate and mucus secretion and mucosal blood flow. The GLP-2 increases bicarbonate secretion via release of vasoactive intestinal peptide (VIP) from myenteric nerves. Luminal bile acids also release gut hormones due to activation of the bile-acid receptor known as G Protein-Coupled Receptor (GPR) 131, G Protein Bile Acid Receptor (GPBAR) 1, or Takeda G Protein-Coupled Receptor (TGR) 5, also expressed on enteroendocrine cells. The GLP are metabolized by dipeptidyl peptidase IV (DPPIV), an enzyme of particular interest to pharmaceutical, because its inhibition increases plasma concentrations of GLP-1 to treat diabetes. We have also reported that DPPIV inhibition enhances the secretory effects of nutrient-evoked GLP-2. Understanding the release mechanism and the metabolic pathways of gut hormones is of potential utility to the formulation of feedstuff additives that, by increasing nutrient absorption due to increased mucosal mass, can increase yields. PUBLICATION ABSTRACT
A reaction plane detector for PHENIX at RHIC Richardson, E.; Akiba, Y.; Anderson, N. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2011, Volume:
636, Issue:
1
Journal Article
Peer reviewed
Open access
A plastic scintillator paddle detector with embedded fiber light guides and photomultiplier tube readout, referred to as the Reaction Plane Detector (RXNP), was designed and installed in the PHENIX ...experiment prior to the 2007 run of the Relativistic Heavy Ion Collider (RHIC). The RXNP's design is optimized to accurately measure the reaction plane (RP) angle of heavy-ion collisions, where, for mid-central sNN=200GeV Au+Au collisions, it achieved a 2nd harmonic RP resolution of ∼0.75, which is a factor of ∼2 greater than PHENIX's previous capabilities. This improvement was accomplished by locating the RXNP in the central region of the PHENIX experiment, where, due to its large coverage in pseudorapidity (1.0<|η|<2.8) and ϕ(2π), it is exposed to the high particle multiplicities needed for an accurate RP measurement. To enhance the observed signal, a 2-cm Pb converter is located between the nominal collision region and the scintillator paddles, allowing neutral particles produced in the heavy-ion collisions to contribute to the signal through conversion electrons. This paper discusses the design, operation and performance of the RXNP during the 2007 RHIC run.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Glucose uptake across the plasma membrane in animal cells plays a crucial role in whole-body glucose homeostasis. Insulin-stimulated glucose transport activity in vivo in several tissues was ...estimated using the 2-deoxy-
d-1-
3Hglucose (
3H2DG) uptake determination method. A tracer dose of
3H2DG was injected intravenously into 8-day-old chicks (
Gallus gallus) administered simultaneously or previously with porcine insulin (40 μg/kg BW). After 10 or 20 min, several major tissues, including skeletal and cardiac muscle, were sampled and their 2-deoxy-
d-1-
3Hglucose 6-phosphate content analyzed. Plasma glucose concentration and
3H2DG radioactivity were lowered by insulin within 20 min of
3H2DG administration, while the plasma
3H2DG/glucose ratio was not significantly different between chicks injected with insulin and their control counterparts. A marked uptake of 2DG was observed in cardiac tissue and brain, followed by kidney and skeletal muscles. In skeletal muscles, insulin increased the 2DG uptake in soleus, extensor digitorum longus and pectoralis superficialis muscles. On the other hand, no significant increases in insulin-induced 2DG uptake were detected in cardiac muscle or adipose tissue compared to controls. The results show that glucose transport across the plasma membrane in vivo in most skeletal muscles tested, but not cardiac muscle, was increased by insulin administration to chicks. These findings suggest that an insulin-responsive glucose transport mechanism is present in chickens, even though they intrinsically lack GLUT4 homologous gene, the insulin-responsive glucose transporter in mammals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The readout of transition-edge sensor (TES) bolometers with a large multiplexing factor is key for the next generation cosmic microwave background (CMB) experiment,
Polarbear
-2 (Suzuki in J Low Temp ...Phys 176:719,
2014
), having 7588 TES bolometers. To enable the large arrays, we have been developing a readout system with a multiplexing factor of 40 in the frequency domain. Extending that architecture to 40 bolometers requires an increase in the bandwidth of the SQUID electronics, above 4 MHz. This paper focuses on cryogenic readout and shows how it affects cross talk and the responsivity of the TES bolometers. A series resistance, such as equivalent series resistance of capacitors for LC filters, leads to non-linear response of the bolometers. A wiring inductance modulates a voltage across the bolometers and causes cross talk. They should be controlled well to reduce systematic errors in CMB observations. We have been developing a cryogenic readout with a low series impedance and have tuned bolometers in the middle of their transition at a high frequency (
>
3 MHz).
Peroxisome proliferatior-activated receptor-gamma (PPARgamma) is a transcription factor that modulates lipid and glucose metabolism in mammals. The aim of the present study was to investigate whether ...chicken PPARgamma is expressed in tissues in a similar manner to mammalian PPAR and whether it is involved in the regulation of lipid metabolism, particularly in the regulation of fat accumulation in adipose tissue and ovaries. In 30-wk-old chickens, PPARgamma mRNA was detected in most tissues that were examined. Of those tissues expressing chicken PPARgamma mRNA, the lowest expression levels were found in adipose tissue, the tissue that in mammals was shown to express the highest levels of PPARgamma mRNA. Chicken PPARgamma mRNA expression in abdominal adipose tissue tended to increase with age, as shown by higher expression levels at 6 wk than at 1 and 2 wk of age. With regard to nutritional modulation, PPARgamma mRNA levels in abdominal adipose tissue were significantly higher in broiler chickens fed for 7 d a diet containing 8% safflower oil (18:2-rich) or linseed oil (18:3-rich) compared with chickens fed a diet containing olive oil (18:1-rich). In contrast, feeding a 3% cholesterol-supplemented diet for 7 d resulted in no changes to adipose PPARgamma mRNA expression. In broiler chickens orally administered troglitazone, a PPARgamma ligand, abdominal fat pad weight and PPARgamma and lipoprotein lipase (LPL) mRNA levels were significantly increased relative to those of control chickens. Levels of PPARgamma mRNA in liver, skeletal muscle, and ovaries were increased with the onset of egg laying, whereas in adipose tissue the level of PPARgamma mRNA was decreased. These findings suggest that PPARgamma plays an important role in the regulation of fat deposition and egg production and the characteristic pattern of PPARgamma mRNA expression may be indicative of specific differences in the lipid and glucose metabolism of chickens compared with mammals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adipocyte differentiation and modulates lipid metabolism in mammals. The aim of the present study was ...to investigate whether the administration of PPARγ ligands, adipogenic cocktail, or both to newly hatched chicks regulates adipocyte differentiation in vivo and modulates fat deposition in growing broiler chickens. Levels of PPARγ, CCAAT/enhancer binding protein α, and adipocyte fatty acid-binding protein mRNA in the abdominal fat pad of 7-d-old broiler chicks given a single intraperitoneal dose of troglitazone, a synthetic PPARγ ligand, at 1 d old were significantly greater than those in control chickens. This suggests administration of troglitazone enhanced adipocyte differentiation in vivo. Adipose tissue weight in 28-d-old chickens similarly administered triolein emulsion containing troglitazone or adipogenic cocktail (i.e., dexamethasone, insulin, isobutyl-methylxanthine, and oleic acid) was also significantly less than that of control chickens. However, there was no significant difference in BW between treated and control chickens. Although BW and carcass composition were not different between troglitazone-treated and control chickens, at 48 d of age abdominal fat pad weight and feed intake were significantly decreased in chickens treated with troglitazone compared with controls. These results demonstrate that a single intraperitoneal injection of troglitazone to newly hatched chicks reduces fat deposition in mature broiler chickens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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