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1.  Role of Neurotransmitter Gases in the Control of the Carotid Body in Heart Failure 
The peripheral arterial chemoreflex, arising primarily from the carotid body in most species, plays an important role in the control of breathing and in autonomic control of cardiovascular function. The peripheral chemoreflex is enhanced in heart failure patients and animal models of heart failure and contributes to the sympathetic hyperactivity and breathing instability that exacerbates the progression of the disease. Studies in animal models have shown that carotid body chemoreceptor activity is enhanced under both normoxic and hypoxic conditions in heart failure due to disruption of local mediators that control carotid body function. This brief review highlights evidence that the alterations in the gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide in the carotid body contribute to the exaggerated carotid body function observed in heart failure.
PMCID: PMC3483421  PMID: 22842006
2.  The synthetic triterpenoid, RTA405, increases glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells 
Kidney international  2012;83(5):845-854.
Bardoxolone methyl, a synthetic triterpenoid, improves the estimated glomerular filtration rate (GFR) in patients with chornic kidney disease and type 2 diabetes. Since the contractile activity of mesangial cells may influence glomerular filtration, we evaluated the effect of the synthetic triterpenoid RTA405 with structural similarity to bardoxolone methyl, on GFR in rats and on mesangial cell contractility in freshly isolated glomeruli. In rats, RTA 405 increased basal GFR, assessed by inulin clearance, and attenuated the angiotensin II-induced decline in GFR. RTA 405 increased the filtration fraction, but did not affect arterial blood pressure or renal plasma flow. Glomeruli from RTA 405-treated rats were resistant to angiotensin II-induced volume reduction ex vivo. In cultured mesangial cells, angiotensin II-stimulated contraction was attenuated by RTA 405, in a dose- and time-dependent fashion. Further, Nrf2 targeted gene transcription (regulates antioxidant, anti-inflammatory, and cytoprotective responses) in mesangial cells was associated with decreased basal and reduced angiotensin II-stimulated hydrogen peroxide and calcium ion levels. These mechanisms contribute to the GFR increase that occurs following treatment with RTA 405 in rats and may underlie the effect of bardoxolone methyl on the estimated GFR in patients.
PMCID: PMC3600401  PMID: 23235569
3.  Simulation of future global warming scenarios in rice paddies with an open-field warming facility 
Plant Methods  2011;7:41.
To simulate expected future global warming, hexagonal arrays of infrared heaters have previously been used to warm open-field canopies of upland crops such as wheat. Through the use of concrete-anchored posts, improved software, overhead wires, extensive grounding, and monitoring with a thermal camera, the technology was safely and reliably extended to paddy rice fields. The system maintained canopy temperature increases within 0.5°C of daytime and nighttime set-point differences of 1.3 and 2.7°C 67% of the time.
PMCID: PMC3264504  PMID: 22145582
Ecosystem warming; climate change; canopy temperature; global change; infrared heating; plant-climate interactions; rice; Yangtze River valley
4.  4,4′-Dibromo-7,7′-dimeth­oxy-1,1′-spiro­biindane 
In the title compound, C19H18Br2O2, the dihedral angle between the two benzene rings of the spiro­biindane molecule is 70.44 (8)°. In the crystal, mol­ecules are inter­connected along the c axis by C—H⋯O hydrogen bonds and π–π stacking [centroid–centroid distance = 3.893 (2) Å] inter­actions, forming an infinite chain structure. The chains are further inter­connected through another set of C—H⋯O hydrogen bonds, forming layers approximately parallel to the bc plane.
PMCID: PMC3011698  PMID: 21589485
5.  Canonical Transient Receptor Potential 6 (TRPC6), a Redox-regulated Cation Channel* 
The Journal of Biological Chemistry  2010;285(30):23466-23476.
This study examined the effect of H2O2 on the TRPC6 channel and its underlying mechanisms using a TRPC6 heterologous expression system. In TRPC6-expressing HEK293T cells, H2O2 significantly stimulated Ca2+ entry in a dose-dependent manner. Electrophysiological experiments showed that H2O2 significantly increased TRPC6 channel open probability and whole-cell currents. H2O2 also evoked a robust inward current in A7r5 vascular smooth muscle cells, which was nearly abolished by knockdown of TRPC6 using a small interfering RNA. Catalase substantially attenuated arginine vasopressin (AVP)-induced Ca2+ entry in cells co-transfected with TRPC6 and AVP V1 receptor. N-Ethylmaleimide and thimerosal were able to simulate the H2O2 response. Dithiothreitol or glutathione-reduced ethyl ester significantly antagonized the response. Furthermore, both N-ethylmaleimide- and H2O2-induced TRPC6 activations were only observed in the cell-attached patches but not in the inside-out patches. Moreover, 1-oleoyl-2-acetyl-sn-glycerol effect on TRPC6 was significantly greater in the presence of H2O2. Biotinylation assays revealed a significant increase in cell surface TRPC6 in response to H2O2. Similarly, in cells transfected with TRPC6-EGFP, confocal microscopy showed a significant increase in fluorescence intensity in the region of the cell membrane and adjacent to the membrane. AVP also increased the fluorescence intensity on the surface of the cells co-transfected with TRPC6-EGFP and V1 receptor, and this response was inhibited by catalase. These data indicate that H2O2 activates TRPC6 channels via modification of thiol groups of intracellular proteins. This cysteine oxidation-dependent pathway not only stimulates the TRPC6 channel by itself but also sensitizes the channels to diacylglycerol and promotes TRPC6 trafficking to the cell surface.
PMCID: PMC2906337  PMID: 20501650
Calcium; Calcium Channels; Calcium Transport; Reactive Oxygen Species (ROS); TRP Channels
6.  Role of CuZn superoxide dismutase on carotid body function in heart failure rabbits 
Cardiovascular Research  2008;81(4):678-685.
Peripheral chemoreflex sensitivity is potentiated in both clinical and experimental chronic heart failure (CHF). NADPH oxidase-derived superoxide mediates angiotensin II (Ang II)-enhanced carotid body (CB) chemoreceptor sensitivity in CHF rabbits, and tempol, the superoxide dismutase (SOD) mimetic, inhibits this Ang II- and CHF-enhanced superoxide anion effect. Here we investigated the role of cytoplasmic SOD [CuZn superoxide dismutase (CuZnSOD)] in the CB on chemoreceptor activity and function in CHF rabbits.
Methods and results
CuZnSOD protein expression was decreased in CBs from CHF rabbits vs. sham (P < 0.05). Adenoviral CuZnSOD (Ad CuZnSOD) gene transfer to the CBs increased CuZnSOD protein expression and significantly reduced the baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in the CHF rabbits (P < 0.05). Single-fibre discharge from CB chemoafferents during normoxia (baseline, at ∼100 mmHg PO2) and in response to hypoxia were enhanced in CHF vs. sham rabbits (P < 0.05). Ad CuZnSOD decreased the baseline discharge (7.6 ± 1.3 vs. 12.6 ± 1.7 imp/s at ∼100 mmHg PO2) and the response to hypoxia (22.4 ± 1.6 vs. 32.3 ± 1.2 imp/s at ∼40 mmHg PO2, P < 0.05) in CHF rabbits. Ad CuZnSOD also normalized the blunted outward K+ current (IK) in CB glomus cells from CHF rabbits (369 ± 14 vs. 565 ± 31 pA/pF at +70 mV, P < 0.05). In addition, Ad CuZnSOD reduced the elevation of superoxide level in CBs from CHF rabbits.
Downregulation of CuZnSOD in the CB contributes to the enhanced activity of CB chemoreceptors and chemoreflex function in CHF rabbits.
PMCID: PMC2642603  PMID: 19091790
Superoxide dismutase; Adenoviral vector; Carotid body; Sympathetic nerve activity; Chemoreceptor; Glomus cell; Chronic heart failure

Results 1-6 (6)