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Two C2H6‐selective metal‐organic framework (MOF) adsorbents with ultrahigh stability, high surface areas, and suitable pore size have been designed and synthesized for one‐step separation of ethane/ethylene (C2H6/C2H4) under humid conditions to produce polymer‐grade pure C2H4. Experimental results reveal that these two MOFs not only adsorb a high amount of C2H6 but also display good C2H6/C2H4 selectivity verified by fixed bed column breakthrough experiments. Most importantly, the good water stability and hydrophobic pore environments make these two MOFs capable of efficiently separating C2H6/C2H4 under humid conditions, exhibiting the benchmark performance among all reported adsorbents for separation of C2H6/C2H4 under humid conditions. Moreover, the affinity sites and their static adsorption energies were successfully revealed by single crystal data and computation studies. Adsorbents described in this work can be used to address major chemical industrial challenges. [ABSTRACT FROM AUTHOR]

Developing new materials for anhydrous proton conduction under high‐temperature conditions is significant and challenging. Herein, we create a series of highly crystalline covalent organic frameworks (COFs) via a pore engineering approach. We simultaneously engineer the pore geometry (generating concave dodecagonal nanopores) and pore surface (installing multiple functional groups such as −C=N−, −OH, −N=N− and −CF3) to improve the utilization efficiency and host–guest interaction of proton carriers, hence benefiting the enhancement of anhydrous proton conduction. Upon loading with H3PO4, COFs can realize a proton conductivity of 2.33×10−2 S cm−1 under anhydrous conditions, among the highest values of all COF materials. These materials demonstrate good stability and maintain high proton conductivity over a wide temperature range (80–160 °C). This work paves a new way for designing COFs for anhydrous proton conduction applications, which shows great potential as high‐temperature proton exchange membranes. [ABSTRACT FROM AUTHOR]

Author(s): David Z. Z. He (corresponding author) [1, 2]; Shuping Jia [1]; Peter Dallos [3] Sensory receptor cells of the mammalian cochlea are morphologically and functionally dichotomized. Inner hair cells [...]

Author(s): M. Charles Liberman [1, 2]; Jiangang Gao [2, 3]; David Z. Z. He [4]; Xudong Wu [3, 5]; Shuping Jia [4]; Jian Zuo (corresponding author) [3] Hearing sensitivity in [...]

The senses of hearing and balance depend upon hair cells, the sensory receptors of the inner ear. Hair cells transduce mechanical stimuli into electrical activity. Loss of hair cells as a result of aging or exposure to noise and ototoxic drugs is the major cause of noncongenital hearing and balance deficits. In the ear of non-mammals, lost hair cells can spontaneously be replaced by production of new hair cells from conversion of supporting cells. Although supporting cells in adult mammals have lost that capability, neonatal supporting cells are able to convert to hair cells after inhibition of Notch signaling. We questioned whether Notch inhibition is sufficient to convert supporting cells to functional hair cells using electrophysiology and electron microscopy. We showed that pharmacological inhibition of the canonical Notch pathway in the cultured organ of Corti prepared from neonatal gerbils induced stereocilia formation in supporting cells (defined as hair cell-like cells or HCLCs) and supernumerary stereocilia in hair cells. The newly emerged stereocilia bundles of HCLCs were functional, i.e., able to respond to mechanical stimulation with mechanotransduction (MET) current. Transmission electron microscopy (TEM) showed that HCLCs converted from pillar cells maintained the pillar cell shape and that subsurface cisternae, normally observed underneath the cytoskeleton in outer hair cells (OHCs), was not present in Deiters' cellsderived HCLCs. Voltage-clamp recordings showed that whole-cell currents from Deiters' cells-derived HCLCs retained the same kinetics and magnitude seen in normal Deiters' cells and that nonlinear capacitance (NLC), an electrical hallmark of OHC electromotility, was not detected from any HCLCs measured. Taken together, these results suggest that while Notch inhibition is sufficient for promoting stereocilia bundle formation, it is insufficient to convert neonatal supporting cells to mature hair cells. The fact that Notch inhibition led to stereocilia formation in supporting cells and supernumerary stereocilia in existing hair cells appears to suggest that Notch signaling may regulate stereocilia formation and stability during development. [ABSTRACT FROM AUTHOR]

R4945 --> 896.3 --> The paraventricular nucleus of the hypothalamus (PVN) is an important autonomic control center. It receives afferent inputs from many brain regions, including the median preoptic nucleus (MnPO). The connection between the MnPO and the PVN is particularly important in generating chronic intermittent hypoxia phenotypes such as increased sympathetic activity leading to the development of hypertension. PVN‐projecting MnPO neurons discharge frequency is <5Hz. To gain more insight into the acute change in PVN neuron properties after low‐frequency stimulation, whole‐cell patch‐clamp recordings were performed on PVN neurons. Adult 250‐350g male rats were injected bilaterally in the PVN with 100 nL retrogradely transported adeno‐associated virus encoding Channelrhodopsin (AAVrg‐CaMKIIa‐hChR2(H134R)‐mCherry) or with AAVrg‐CAG‐tdTomato as control. Three weeks after the injections, the rats were anesthetized with isoflurane (2‐3%) and sacrificed to prepare horizontal brain slices containing the PVN and MnPO. Postsynaptic currents were recorded from PVN neurons in whole‐cell voltage clamp configuration (Vhold=‐60 mV) under constant bath perfusion of normal aCSF (2‐3 ml/min). Axon terminals in the PVN were stimulated with 5Hz LED‐generated blue light (470nM) pulses of 50‐ms duration, 5 seconds off/on for a total of 1 min, delivered using optical fiber directed to the MnPO. Photo‐evoked currents were measured during 5 min before and after the photo‐stimulation train. Amplitude and frequency of spontaneous currents were compared before and after stimulation as well. At the end of each recording, cells were characterized as type I (magnocellular) or type II (parvocellular) PVN neurons based on the presence of transient outward rectification. Data were analyzed offline using Easy Electrophysiology v2.3.3 software. For both cell types, 5 Hz optogenetic stimulation caused a significant reduction in the optogenetic‐evoked current amplitude during the first 15 minutes after stimulation (before stimulation 94.88±2.85 %, n=9 cells vs. 15 minutes after stimulation 67.52±6.15 %, n=9. P=0.0027) before returning to baseline values. Post‐stimulation spontaneous postsynaptic current amplitude and frequency decreased in type II PVN neurons from retrograde ChR2 animals (pre‐stimulation amplitude 100±0.62 % vs. post‐stimulation amplitude 86.50±0.54 %, P=0.0371; pre‐stimulation frequency 3.82±1.7 Hz, post‐stimulation frequency 2.396±1.2 Hz, P= 0.0385) but not in type I PVN neurons from retrograde ChR2 animals or cells from control animals. Kinetic profiles of spontaneous current in type I and II PVN neurons did not change after 5 Hz optogenetic stimulation. The results suggest that low‐frequency stimulation discriminately alters spontaneous presynaptic neurotransmitter release and possibly postsynaptic responsiveness in PVN neurons. Additional experiments will be needed to specifically stimulate PVN afferents from the MnPO. [ABSTRACT FROM AUTHOR]

R4328 --> 896.2 --> Chronic intermittent hypoxia (CIH) has been shown to alter the response of neurons in Median Preoptic nucleus (MnPO) to activation of cardiovascular inputs. Our previous results indicate that CIH enhances spontaneous presynaptic neurotransmitter release while also increasing postsynaptic responsiveness in MnPO. In other systems, BNDF/TrkB signaling has been shown to facilitate excitatory neurotransmission, so we tested its role in the increased MnPO excitation triggered by CIH. Data were collected from PVN‐projecting MnPO neurons which play an important role in CIH‐induced hypertension. Adult 250‐350g male rats were injected bilaterally in the PVN with 200 nL retrograde adeno‐associated virus (pAAV‐CAG‐tdTomato). Three weeks after the injections, the rats were exposed to a 7‐day intermittent hypoxia protocol (6 min cycles; 3 minutes of 21% oxygen, 3 min of 10% oxygen maintenance at 10% oxygen for 8 h during the light phase). Normoxic controls were exposed to room air. At the end of the protocol, the rats were anesthetized with isoflurane (2‐3%) and horizontal brain slices of MnPO were prepared. Miniature Excitatory Postsynaptic Currents (mEPSCs) were recorded using whole cell voltage clamp configuration from PVN‐projecting MnPO neurons. The mEPSCs were recorded with the holding potential of ‐60 mV in the presence of a GABAa receptor antagonist (SR 95531 hydrobromide, 25 µM), tetrodotoxin (1µM), and a glycine receptor antagonist (strychnine, 3 µM) in aCSF. Data were analyzed off‐line using Synaptosoft software. Differences in mEPSCs properties, such as peak amplitude, frequency, decay time, area, and cell capacitance were analyzed by ANOVA and Tukey multiple comparison tests. The results showed that CIH significantly increased mEPSCs frequency (Hz: CIH 1.32 ± 0.09 vs Norm 0.83 ± 0.09, p=5E‐04), decay time (ms: CIH 8.01 ± 0.28 vs Norm 6.64 ± 0.36, p=0.004), area (pA.ms: CIH 63.85± 3.65 vs Norm 50.27 ± 3.6, p=0.01), and cell capacitance (pF: CIH 31.55 ± 1.8 vs Norm 25.34 ± 1.95, p=0.02). The contribution of BDNF/TrkB signaling to these CIH effects were tested using K252a and K252b, two structurally related kinase receptor inhibitors. MnPO slices were pre‐incubated with either K252a or K252b (200nM) for 30 min before recording. Neither K252a nor K252b influenced mEPSCs of MnPO neurons from normoxic slices. Both K252a and K252b significantly affected CIH‐induced changes mEPSCs but at different magnitudes. The K252a significantly reduced the effects of CIH on frequency (Hz: K252a 0.46 ± 0.05, p=1E‐08), decay time (ms: K252a 6.07 ± 0.34, p=1E‐04), area (pA.ms: K252a 43.26 ± 3.55, p=5E‐04), and cell capacitance (pF: K252a 19.59 ± 1.61, p=1E‐04;). In addition, K252a also significantly decreased mEPSCs peak amplitude in CIH neurons (pA: CIH 14.87 ± 0.41 vs K252a 13.27 ± 0.39, p=0.03). While K252b pretreatment also affected the same parameters, the changes produced by K252a were significantly greater. These studies suggest a role for BDNF/TrkB signaling in CIH induced changes in MnPO but additional experiments will be required to validate the specificity of our results. [ABSTRACT FROM AUTHOR]

The remarkable sensitivity and frequency selectivity of the mammalian cochlea is attributed to a unique amplification process that resides in outer hair cells (OHCs). Although the mammalian-specific somatic motility is considered a substrate of cochlear amplification, it has also been proposed that somatic motility in mammals simply acts as an operating-point adjustment for the ubiquitous stereocilia-based amplifier. To address this issue, we created a mouse model in which a mutation (Cl) was introduced into the OHC motor protein prestin, based on previous results in transfected cells. In Cl/Cl knockin mice, localization of Ci-prestin, as well as the length and number of OHCs, were all normal. In OHCs isolated from Cl/Cl mice, nonlinear capacitance and somatic motility were both shifted toward hyperpolarization, so that, compared with WT controls, the amplitude of cycle-by- cycle (alternating, or AC) somatic motility remained the same, but the unidirectional (DC) component reversed polarity near the OHC's presumed in vivo resting membrane potential. No physiological defects in cochlear sensitivity or frequency selectivity were detected in Cl/Cl or C1/+ mice. Hence, our results do not support the idea that OHC somatic motility adjusts the operating point of a stereocilia-based amplifier. However, they are consistent with the notion that the AC component of OHC somatic motility plays a dominant role in mammalian cochlear amplification. [ABSTRACT FROM AUTHOR]

R3592 --> Studies have shown that the median preoptic nucleus (MnPO) contributes to hypertension associated with chronic intermittent hypoxia (CIH), a model of the hypoxemia associated with sleep apnea. Virally mediated lesions of MnPO neurons prevent the development of a sustained hypertension associated with CIH. To gain more insight into the properties of excitatory transmission to MnPO neurons develops in CIH, whole cell patch clamp recordings were from MnPO neurons brain slices from rats exposed to 7 days of CIH (6 minute cycles; 3 minutes of 21% oxygen room air pumped in, 90 seconds of nitrogen pumped in to lower the chamber O2 to 10% oxygen, and then 90 seconds of maintenance at 10% oxygen) for 8 h during the light phase or were normoxic controls. Slices were perfused with oxygenates artificial cerebrospinal fluid and the MnPO was visually identified. Miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presences of 25 µm SR95531 (GABAA antagonist) and 1 µm TTX (block Na+ channel‐mediated action potentials) using a conventional whole cell patch clamp configuration. The mEPSCs were collected over a 4 min period and amplitude and frequency were compared between cells obtained from slice prepared from normoxic control rats (NORM) or rats exposed to CIH. CIH was associated with a significant increase in mean amplitude (CIH 17.15 ± 0.65 pA, n=19 cells; NORM (15.6 ± 0.6 pA; n=18 cells, P <0.05). Similarly, mean frequency was significantly elevated after CIH (CIH 4.05 ± 0.5 Hz, n=19 vs NORM 2.56 ± 0.37 Hz, n=18; p<0.05) and associated with a significant leftward shift in the cumulative probability of inter event intervals. The results suggest that CIH simultaneously increases enhances spontaneous presynaptic neurotransmitter release while also increasing postsynaptic responsiveness in MnPO. These presynaptic and postsynaptic changes in MnPO that are associated with CIH may represent mechanism contributing to CIH hypertension. [ABSTRACT FROM AUTHOR]

Abstract: Prestin is the motor protein of cochlear outer hair cells (OHCs) with the unique capability of performing direct, rapid, and reciprocal electromechanical conversion. Prestin consists of 744 amino acids with a molecular mass of ∼81.4kDa. The predicted membrane topology and molecular mass of a single prestin molecule appear inadequate to account for the size of intramembrane particles (IMPs) expressed in the OHC membrane. Although recent biochemical evidence suggests that prestin forms homo-oligomers, most likely as a tetramer, the oligomeric structure of prestin in OHCs remains unclear. We obtained the charge density of prestin in the gerbil OHCs by measuring their nonlinear capacitance (NLC). The average charge density (22,608μm− 2) measured was four times the average IMP density (5686μm− 2) reported in the freeze-fracture study. This suggests that each IMP contains four prestin molecules, based on the general notion that each prestin transfers a single elementary charge. We subsequently compared the voltage dependency and the values of slope factor of NLC and somatic motility simultaneously measured from the same OHCs to determine whether NLC and motility are fully coupled and how prestin subunits function within the tetramer. We showed that the voltage dependency and slope factors of NLC and motility were not statistically different, suggesting that NLC and motility are fully coupled. The fact that the slope factor is the same between NLC and motility suggests that each prestin monomer in the tetramer is in parallel, each interacting independently with cytoplasmic or other partners to facilitate the mechanical response. [Copyright &y& Elsevier]

Abstract: Glucose transporter 5 (Glut5) is a high-affinity fructose transporter. It was proposed to be a motor protein or part of the motor complex required for cochlear amplification in outer hair cells (OHCs). Here we show that, in contrast to previous reports, Glut5 is undetectable, and possibly absent, in OHCs harvested from wildtype mice. Further, Glut5-deficient mice display normal OHC morphology and motor function (i.e., nonlinear capacitance and electromotility) and normal cochlear sensitivity and frequency selectivity. We conclude that Glut5 is not required for OHC motility or cochlear amplification. [Copyright &y& Elsevier]

Summary: It is a central tenet of cochlear neurobiology that mammalian ears rely on a local, mechanical amplification process for their high sensitivity and sharp frequency selectivity. While it is generally agreed that outer hair cells provide the amplification, two mechanisms have been proposed: stereociliary motility and somatic motility. The latter is driven by the motor protein prestin. Electrophysiological phenotyping of a prestin knockout mouse intimated that somatic motility is the amplifier. However, outer hair cells of knockout mice have significantly altered mechanical properties, making this mouse model unsatisfactory. Here, we study a mouse model without alteration to outer hair cell and organ of Corti mechanics or to mechanoelectric transduction, but with diminished prestin function. These animals have knockout-like behavior, demonstrating that prestin-based electromotility is required for cochlear amplification. [Copyright &y& Elsevier]