Long-Acting Real-Time Microscopic Monitoring Inside the Proton Exchange Membrane Water Electrolyzer.

The proton exchange membrane water electrolyzer (PEMWE) requires a high operating voltage for hydrogen production to accelerate the decomposition of hydrogen molecules so that the PEMWE ages or fails. According to the prior findings of this R&D team, temperature and voltage can influence the performance or aging of PEMWE. As the PEMWE ages inside, the nonuniform flow distribution results in large temperature differences, current density drops, and runner plate corrosion. The mechanical stress and thermal stress resulting from pressure distribution nonuniformity will induce the local aging or failure of PEMWE. The authors of this study used gold etchant for etching, and acetone was used for the lift-off part. The wet etching method has the risk of over-etching, and the cost of the etching solution is also higher than that of acetone. Therefore, the authors of this experiment adopted a lift-off process. Using the flexible seven-in-one (voltage, current, temperature, humidity, flow, pressure, oxygen) microsensor developed by our team, after optimized design, fabrication, and reliability testing, it was embedded in PEMWE for 200 h. The results of our accelerated aging test prove that these physical factors affect the aging of PEMWE.

A study of tryptophan, kynurenine and serotonin transporter in first-episode drug-naïve major depressive disorder.

Major depressive disorder (MDD) is associated with the disharmonic functioning of the serotonin system. The serotonin system is mainly modulated by the serotonin transporter (SERT) which regulates serotonin uptake and the metabolism of its precursor, tryptophan and following kynurenine pathway. Currently, there is a lack of research examining both markers concurrently in MDD. This study evaluated the alterations and inter-relationships of both markers in first-episode drug-naïve MDD patients. Thirty-three MDD patients and 33 age- and sex-matched healthy controls (HC) were recruited. The SERT availability were comparable between two groups in the midbrain, thalamus, caudate, and putamen. The kynurenine/tryptophan ratio which indicates tryptophan metabolism was lower in MDD than HC with no group difference in the tryptophan or kynurenine concentration. A negative correlation between the midbrain SERT availability and kynurenine concentration in HC was found. For the subgroup of HC with high kynurenine/tryptophan ratio, the SERT availability was positively associated with the kynurenine/tryptophan ratio and negatively correlated with tryptophan or kynurenine concentration. This study demonstrated the altered tryptophan metabolism and the relationship between tryptophan metabolism and the SERT availability in first-episode drug-naïve MDD patients, which gave a new insight towards the future investigation of the pathophysiology of MDD.

Standing 8-Electrode Bioelectrical Impedance Analysis as an Alternative Method to Estimate Visceral Fat Area and Body Fat Mass in Athletes.

PURPOSE: To investigate the potential of standing 8-electrode bioelectrical impedance analysis (BIA) for assessing visceral fat area (VFA) and body fat mass (BFM) in athletes. MATERIALS AND METHODS: A total of 95 subjects (50 males and 45 females) were recruited. VFA and BFM measurements were obtained using three standing 8-electrode BIA devices, InBody230, InBody770, and IOI353. These acquired VFA and BFM were expressed as VFAIOI353, VFAInBody230, VFAInBody770 V, BFMIOI353, BFMInBody230, and BFMInBody770, respectively. As reference measurement, the VFA acquired from computer tomography (CT) was expressed as VFACT, and the BFM measured by dual-energy X-ray absorptiometry (DXA) was denoted as BFMDXA. RESULTS: The coefficient of determination (r2) in regression analysis between the measurements by VFAIOI353, VFAInBody230, VFAInBody770 and VFACT were 0.425, 0.492, and 0.473, respectively. Also, the limits of agreement (LOA) obtained from Bland-Altman analysis were -25.18 to 56.62, -29.74 to 62.44, and -32.96 to 71.93 cm2. For BFM, r2 in regression analysis between the measurements by BFMIOI353, BFMInBody230, BFMInBody770 and BMFDXA were 0.894, 0.950, and 0.955, respectively; LOA were -7.21 to 5.75, -4.70 to 4.05, and -5.48 to 3.05 kg, respectively. CONCLUSION: The results showed when assessing BFM, these instruments delivered comparable measurements, and the degree of agreement ranged from excellent to moderate compared with the reference method. However, when assessing VFA, the agreements were weak. Therefore, the application of standing 8-electrode BIA devices for assessing athletes' VFA still needs improvement.

Neither cortisol nor brain-derived neurotrophic factor is associated with serotonin transporter in bipolar disorder.

Converging evidence indicates the hypothalamus-pituitary-adrenal axis and serotonergic neurons exert reciprocal modulatory actions. Likewise, brain-derived neurotrophic factor (BDNF) has been implicated as a growth and differentiation factor in the development of serotonergic neurons. The aim of this study was to examine the interaction of cortisol and BDNF on serotonin transporter (SERT) in bipolar disorder (BD). Twenty-eight BD and 28 age- and gender-matched healthy controls (HCs) were recruited. (123)I-ADAM with single-photon emission computed tomography (SPECT) was applied for measurement of SERT availability in the brain, which included the midbrain, thalamus, putamen and caudate. Ten milliliters of venous blood was withdrawn, when the subject underwent SPECT, for the measurement of the plasma concentration of cortisol and BDNF. SERT availability was significantly decreased in the midbrain and caudate of BD compared with HCs, whereas plasma concentration of cortisol and BDNF did not show a significant difference. The linear mixed-effect model revealed that there was a significant interaction of group and cortisol on SERT availability of the midbrain, but not BDNF. Linear regression analyses by groups revealed that cortisol was associated with SERT availability in the midbrain in the HCs, but not in BD. Considering previous studies, which showed a significant association of cortisol with SERT availability in the HCs and major depressive disorder (MDD), our result replicated a similar finding in HCs. However, the negative finding of the association of cortisol and SERT availability in BD, which was different from MDD, suggests a different role for cortisol in the pathophysiology of mood disorder.

Chest-Worn Health Monitor Based on a Bistatic Self-Injection-Locked Radar.

This paper presents wearable health monitors that are based on continuous-wave Doppler radar technology. To achieve low complexity, low power consumption, and simultaneous wireless transmission of Doppler information, the radar architecture is bistatic with a self-injection-locked oscillator (SILO) tag and an injection-locked oscillator (ILO)-based frequency demodulator. In experiments with a prototype that was operated in the medical body area network and the industrial scientific and medical bands from 2.36 to 2.484 GHz, the SILO tag is attached to the chest of a subject to transform the movement of the chest due to cardiopulmonary activity and body exercise into a transmitted frequency-modulated wave. The tag consumes a very low power of 4.4 mW. The ILO-based frequency demodulator, located 30 cm from the subject, receives and processes this wave to yield the waveform that is associated with the movement of the chest. Following further digital signal processing, the cardiopulmonary activity and body exercise are displayed as time-frequency spectrograms. Promisingly, the experimental results that are presented in this paper reveal that the proposed health monitor has high potential to integrate a cardiopulmonary sensor, a pedometer, and a wireless transmission device on a single radar platform.

Mu opioid receptor stimulation activates c-Jun N-terminal kinase 2 by distinct arrestin-dependent and independent mechanisms.

G protein-coupled receptor desensitization is typically mediated by receptor phosphorylation by G protein-coupled receptor kinase (GRK) and subsequent arrestin binding; morphine, however, was previously found to activate a c-Jun N-terminal kinase (JNK)-dependent, GRK/arrestin-independent pathway to produce mu opioid receptor (MOR) inactivation in spinally-mediated, acute anti-nociceptive responses [Melief et al.] [1]. In the current study, we determined that JNK2 was also required for centrally-mediated analgesic tolerance to morphine using the hotplate assay. We compared JNK activation by morphine and fentanyl in JNK1(-/-), JNK2(-/-), JNK3(-/-), and GRK3(-/-) mice and found that both compounds specifically activate JNK2 in vivo; however, fentanyl activation of JNK2 was GRK3-dependent, whereas morphine activation of JNK2 was GRK3-independent. In MOR-GFP expressing HEK293 cells, treatment with either arrestin siRNA, the Src family kinase inhibitor PP2, or the protein kinase C (PKC) inhibitor Gö6976 indicated that morphine activated JNK2 through an arrestin-independent Src- and PKC-dependent mechanism, whereas fentanyl activated JNK2 through a Src-GRK3/arrestin-2-dependent and PKC-independent mechanism. This study resolves distinct ligand-directed mechanisms of JNK activation by mu opioid agonists and understanding ligand-directed signaling at MOR may improve opioid therapeutics.

Kinetic and structural studies on the catalytic role of the aspartic acid residue conserved in copper amine oxidase.

Copper amine oxidase contains a post-translationally generated quinone cofactor, topa quinone (TPQ), which mediates electron transfer from the amine substrate to molecular oxygen. The overall catalytic reaction is divided into the former reductive and the latter oxidative half-reactions based on the redox state of TPQ. In the reductive half-reaction, substrate amine reacts with the C5 carbonyl group of the oxidized TPQ, forming the substrate Schiff base (TPQ(ssb)), which is then converted to the product Schiff base (TPQ(psb)). During this step, an invariant Asp residue with an elevated pKa is presumed to serve as a general base accepting the alpha proton of the substrate. When Asp298, the putative active-site base in the recombinant enzyme from Arthrobacter globiformis, was mutated into Ala, the catalytic efficiency dropped to a level of about 10(6) orders of magnitude smaller than the wild-type (WT) enzyme, consistent with the essentiality of Asp298. Global analysis of the slow UV/vis spectral changes observed during the reductive half-reaction of the D298A mutant with 2-phenylethylamine provided apparent rate constants for the formation and decay of TPQ(ssb) (k(obs) = 4.7 and 4.8 x 10(-4) s(-1), respectively), both of which are markedly smaller than those of the WT enzyme determined by rapid-scan stopped-flow analysis (k(obs) = 699 and 411 s(-1), respectively). Thus, Asp298 plays important roles not only in the alpha-proton abstraction from TPQ(ssb) but also in other steps in the reductive half-reaction. X-ray diffraction analyses of D298A crystals soaked with the substrate for 1 h and 1 week revealed the structures of TPQ(ssb) and TPQ(psb), respectively, as pre-assigned by single-crystal microspectrophotometry. Consistent with the stereospecificity of alpha-proton abstraction, the pro-S alpha-proton of TPQ(ssb) to be abstracted is positioned nearly perpendicularly to the plane formed by the Schiff-base imine double bond conjugating with the quinone ring of TPQ, so that the orbitals of sigma and pi electrons maximally overlap in the conjugate system. More intriguingly, the pro-S alpha proton of the substrate is released stereospecifically even in the reaction catalyzed by the base-lacking D298A mutant. On the basis of these results, we propose that the stereospecificity of alpha-proton abstraction is primarily determined by the conformation of TPQ(ssb), rather than the relative geometry of TPQ and the catalytic base.

Reinvestigation of metal ion specificity for quinone cofactor biogenesis in bacterial copper amine oxidase.

The topa quinone (TPQ) cofactor of copper amine oxidase is generated by copper-assisted self-processing of the precursor protein. Metal ion specificity for TPQ biogenesis has been reinvestigated with the recombinant phenylethylamine oxidase from Arthrobacter globiformis. Besides Cu2+ ion, some divalent metal ions such as Co2+, Ni2+, and Zn2+ were also bound to the metal site of the apoenzyme so tightly that they were not replaced by excess Cu2+ ions added subsequently. Although these noncupric metal ions could not initiate TPQ formation under the atmospheric conditions, we observed slow spectral changes in the enzyme bound with Co2+ or Ni2+ ion under the dioxygen-saturating conditions. Resonance Raman spectroscopy and titration with phenylhydrazine provided unambiguous evidence for TPQ formation by Co2+ and Ni2+ ions. Steady-state kinetic analysis showed that the enzymes activated by Co2+ and Ni2+ ions were indistinguishable from the corresponding metal-substituted enzymes prepared from the native copper enzyme (Kishishita, S., Okajima, T., Kim, M., Yamaguchi, H., Hirota, S., Suzuki, S., Kuroda, S., Tanizawa, K., and Mure, M. (2003) J. Am. Chem. Soc. 125, 1041-1055). X-ray crystallographic analysis has also revealed structural identity of the active sites of Co- and Ni-activated enzymes with Cu-enzyme. Thus Cu2+ ion is not the sole metal ion assisting TPQ formation. Co2+ and Ni2+ ions are also capable of forming TPQ, though much less efficiently than Cu2+.