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Item Human SLC4A11 Is a Novel NH3/H+ Co-transporter(American Society for Biochemistry and Molecular Biology, 2015-07-03) Zhang, Wenlin; Ogando, Diego G.; Bonanno, Joseph A.; Obukhov, Alexander G.; Department of Cellular & Integrative Physiology, IU School of MedicineSLC4A11 has been proposed to be an electrogenic membrane transporter, permeable to Na(+), H(+) (OH(-)), bicarbonate, borate, and NH4 (+). Recent studies indicate, however, that neither bicarbonate or borate is a substrate. Here, we examined potential NH4 (+), Na(+), and H(+) contributions to electrogenic ion transport through SLC4A11 stably expressed in Na(+)/H(+) exchanger-deficient PS120 fibroblasts. Inward currents observed during exposure to NH4Cl were determined by the [NH3]o, not [NH4 (+)]o, and current amplitudes varied with the [H(+)] gradient. These currents were relatively unaffected by removal of Na(+), K(+), or Cl(-) from the bath but could be reduced by inclusion of NH4Cl in the pipette solution. Bath pH changes alone did not generate significant currents through SLC4A11, except immediately following exposure to NH4Cl. Reversal potential shifts in response to changing [NH3]o and pHo suggested an NH3/H(+)-coupled transport mode for SLC4A11. Proton flux through SLC4A11 in the absence of ammonia was relatively small, suggesting that ammonia transport is of more physiological relevance. Methylammonia produced currents similar to NH3 but with reduced amplitude. Estimated stoichiometry of SLC4A11 transport was 1:2 (NH3/H(+)). NH3-dependent currents were insensitive to 10 μM ethyl-isopropyl amiloride or 100 μM 4,4'- diisothiocyanatostilbene-2,2'-disulfonic acid. We propose that SLC4A11 is an NH3/2H(+) co-transporter exhibiting unique characteristics.Item Integrated micro PEM fuel cell with self-regulated hydrogen generation from ammonia borane(2015-08) Zamani Farahani, Mahmoud Reza; Zhu, LikunAn integrated micro PEM fuel cell system with self-regulated hydrogen generation from ammonia borane is reported to power portable electronics. Hydrogen is generated via catalytic hydrolysis reaction of ammonia borane solution in microchannels with nanoporous platinum catalyst electroplated inside the microchannels. The self-regulation of the ammonia borane solution is achieved by using directional growth and selective venting of hydrogen bubbles in microchannels, which leads to agitation and addition of fresh solution without power consumption. The device is fabricated on combination of polystyrene sheets cut by graphic cutter, a stainless steel layer cut using wire electrical discharge machining and bonding layers with double-sided polyimide tape. Due to the seamless bonding between the hydrogen generator and the micro fuel cell, the dead volume in the gas connection loops can be significantly reduced and the response time of self-regulation is reduced.Item Peripheral ammonia and blood brain barrier structure and function after methamphetamine(Elsevier, 2016-08) Northrop, Nicole A.; Halpin, Laura E.; Yamamoto, Bryan K.; Department of Pharmacology and Toxicology, IU School of MedicineAn effect of the widely abuse psychostimulant, methamphetamine (Meth), is blood-brain-barrier (BBB) disruption; however, the mechanism by which Meth causes BBB disruption remains unclear. Recently it has been shown that Meth produces liver damage and consequent increases in plasma ammonia. Ammonia can mediate oxidative stress and inflammation, both of which are known to cause BBB disruption. Therefore, the current studies examined the role of peripheral ammonia in Meth-induced disruption of BBB structure and function. A neurotoxic Meth regimen (10 mg/kg, ip, q 2 h, ×4) administered to rats increased plasma ammonia and active MMP-9 in the cortex 2 h after the last Meth injection, compared to saline treated rats. At 24 h after Meth treatment, decreased immunoreactivity of BBB structural proteins, occludin and claudin-5, and increased extravasation of 10,000 Da FITC-dextran were observed, as compared to saline controls. Pretreatment with lactulose (5.3 g/kg, po, q 12 h), a drug that remains in the lumen of the intestine and promotes ammonia excretion, prevented the Meth-induced increases in plasma ammonia. These results were paralleled by the prevention of decreases in BBB structural proteins, increases in extravasation of 10,000 Da FITC-dextran and increases in active MMP-9. The results indicate that Meth-induced increases in ammonia produce BBB disruption and suggest that MMP-9 activation mediates the BBB disruption. These findings identify a novel mechanism of Meth-induced BBB disruption that is mediated by plasma ammonia and are the first to identify a peripheral contribution to Meth-induced BBB disruption.