Electrogenic transport and K(+) ion channel expression by the human endolymphatic sac epithelium.

The endolymphatic sac (ES) is a cystic organ that is a part of the inner ear and is connected to the cochlea and vestibule. The ES is thought to be involved in inner ear ion homeostasis and fluid volume regulation for the maintenance of hearing and balance function. Many ion channels, transporters, and exchangers have been identified in the ES luminal epithelium, mainly in animal studies, but there has been no functional study investigating ion transport using human ES tissue. We designed the first functional experiments on electrogenic transport in human ES and investigated the contribution of K(+) channels in the electrogenic transport, which has been rarely identified, even in animal studies, using electrophysiological/pharmacological and molecular biological methods. As a result, we identified functional and molecular evidence for the essential participation of K(+) channels in the electrogenic transport of human ES epithelium. The identified K(+) channels involved in the electrogenic transport were KCNN2, KCNJ14, KCNK2, and KCNK6, and the K(+) transports via those channels are thought to play an important role in the maintenance of the unique ionic milieu of the inner ear fluid

Supersymmetric quantum mechanics with nonlocal potentials

We consider supersymmetric quantum mechanical models with both local and nonlocal potentials. We present a nonlocal deformation of exactly solvable local models. Its energy eigenfunctions and eigenvalues are determined exactly. We observe that both our model Hamiltonian and its supersymmetric partner may have normalizable zero-energy ground states, in contrast to local models with nonperiodic or periodic potentials.Comment: 4 pages, REVTeX, Minor revisions for clarificatio

Critical Behavior of Frustrated Josephson Junction Arrays with Bond Disorder

The scaling behavior of the current-voltage ($IV$) characteristics of a two-dimensional proximity-coupled Josephson junction array (JJA) with quenched bond disorder was investigated for frustrations $f=1/5$, 1/3, 2/5, and 1/2. For all these frustrations including 1/5 and 2/5 where a strongly first-order phase transition is expected in the absence of disorder, the $IV$ characteristics exhibited a good scaling behavior. The critical exponent $\nu$ indicates that bond disorder may drive the phase transitions of frustrated JJA's to be continuous but not into the Ising universality class, contrary to what was observed in Monte Carlo simulations. The dynamic critical exponent $z$ for JJA's was found to be only 0.60 - 0.77.Comment: RevTeX4, 4 pages, 4 figures, the manuscript is replaced with the published versio

Network-Level Structural Abnormalities of Cerebral Cortex in Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion. © 2013 Lyoo et al

Calcium-binding Protein Calretinin Immunoreactivity in the Dog Superior Colliculus

We studied calretinin-immunoreactive (IR) fibers and cells in the canine superior colliculus (SC) and studied the distribution and effect of enucleation on the distribution of this protein. Localization of calretinin was immunocytochemically observed. A dense plexus of anti-­calretinin-IR fibers was found within the upper part of the superficial gray layer (SGL). Almost all of the labeled fibers were small in diameter with few varicosities. The intermediate and deep layers contained many calretinin-IR neurons. Labeled neurons within the intermediate gray layer (IGL) formed clusters in many sections. By contrast, labeled neurons in the deep gray layer (DGL) did not form clusters. Calretinin-IR neurons in the IGL and DGL varied in morphology and included round/oval, vertical fusiform, stellate, and horizontal neurons. Neurons with varicose dendrites were also labeled in the IGL. Most of the labeled neurons were small to medium in size. Monocular enucleation produced an almost complete reduction of calretinin-IR fibers in the SC contralateral to the enucleation. However, many calretinin-IR cells appeared in the contralateral superficial SC. Enucleation appeared to have no effect on the distribution of calretinin-IR neurons in the contralateral intermediate and deep layers of the SC. The calretinin-IR neurons in the superficial dog SC were heterogeneous small- to medium-sized neurons including round/oval, vertical fusiform, stellate, pyriform, and ­horizontal in shape. Two-color immunofluorescence revealed that no cells in the dog SC ­expressed both calretinin and GABA. Many horseradish peroxidase (HRP)-labeled retinal ganglion cells were seen after injections into the superficial layers. The vast majority of the double-labeled cells (HRP and calretinin) were small cells. The present results indicate that antibody to calretinin labels subpopulations of neurons in the dog SC, which do not express GABA. The results also suggest that the calretinin-IR afferents in the superficial layers of the dog SC originate from small class retinal ganglion cells. The expression of calretinin might be changed by the cellular activity of selective superficial collicular neurons. These results are valuable in delineating the basic neurochemical architecture of the dog visual system

Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases

BACKGROUND: Despite aggressive treatment with radiation therapy and concurrent adjuvant temozolomide (TMZ), glioblastoma multiform (GBM) still has a dismal prognosis. We aimed to identify strategies to improve the therapeutic outcome of combined radiotherapy and TMZ in GBM by targeting pro-survival signaling from the epidermal growth factor receptor (EGFR). METHODS: Glioma cell lines U251, T98G were used. Colony formation, DNA damage repair, mode of cell death, invasion, migration and vasculogenic mimicry as well as protein expression were determined. RESULTS: U251 cells showing a low level of methyl guanine transferase (MGMT) were highly responsive to the radiosensitizing effect of TMZ compared to T98G cells having a high level of MGMT. Treatment with a dual inhibitor of Class I PI3K/mTOR, PI103; a HSP90 inhibitor, 17-DMAG; or a HDAC inhibitor, LBH589, further increased the cytotoxic effect of radiation therapy plus TMZ in U251 cells than in T98G cells. However, treatment with a mTOR inhibitor, rapamycin, did not discernibly potentiate the radiosensitizing effect of TMZ in either cell line. The mechanism of enhanced radiosensitizing effects of TMZ was multifactorial, involving impaired DNA damage repair, induction of autophagy or apoptosis, and reversion of EMT (epithelial-mesenchymal transition). CONCLUSIONS: Our results suggest possible strategies for counteracting the pro-survival signaling from EGFR to improve the therapeutic outcome of combined radiotherapy and TMZ for high-grade gliomas

Plug-in nanoliter pneumatic liquid dispenser with nozzle design flexibility

This paper presents a novel plug-in nanoliter liquid dispensing system with a plugand-play interface for simple and reversible, yet robust integration of the dispenser. A plug-in type dispenser was developed to facilitate assembly and disassembly with an actuating part through efficient modularization. The entire process for assembly and operation of the plug-in dispenser is performed via the plug-and-play interface in less than a minute without loss of dispensing quality. The minimum volume of droplets pneumatically dispensed using the plug-in dispenser was 124 nl with a coefficient of variation of 1.6%. The dispensed volume increased linearly with the nozzle size. Utilizing this linear relationship, two types of multinozzle dispensers consisting of six parallel channels (emerging from an inlet) and six nozzles were developed to demonstrate a novel strategy for volume gradient dispensing at a single operating condition. The droplet volume dispensed from each nozzle also increased linearly with nozzle size, demonstrating that nozzle size is a dominant factor on dispensed volume, even for multinozzle dispensing. Therefore, the proposed plug-in dispenser enables flexible design of nozzles and reversible integration to dispense droplets with different volumes, depending on the application. Furthermore, to demonstrate the practicality of the proposed dispensing system, we developed a pencil-type dispensing system as an alternative to a conventional pipette for rapid and reliable dispensing of minute volume droplets. (C) 2015 AIP Publishing LLC.open114sciescopu

Frustrated two-dimensional Josephson junction array near incommensurability

To study the properties of frustrated two-dimensional Josephson junction arrays near incommensurability, we examine the current-voltage characteristics of a square proximity-coupled Josephson junction array at a sequence of frustrations f=3/8, 8/21, 0.382 $(\approx (3-\sqrt{5})/2)$, 2/5, and 5/12. Detailed scaling analyses of the current-voltage characteristics reveal approximately universal scaling behaviors for f=3/8, 8/21, 0.382, and 2/5. The approximately universal scaling behaviors and high superconducting transition temperatures indicate that both the nature of the superconducting transition and the vortex configuration near the transition at the high-order rational frustrations f=3/8, 8/21, and 0.382 are similar to those at the nearby simple frustration f=2/5. This finding suggests that the behaviors of Josephson junction arrays in the wide range of frustrations might be understood from those of a few simple rational frustrations.Comment: RevTex4, 4 pages, 4 eps figures, to appear in Phys. Rev.

Collider and Dark Matter Phenomenology of Models with Mirage Unification

We examine supersymmetric models with mixed modulus-anomaly mediated SUSY breaking (MM-AMSB) soft terms which get comparable contributions to SUSY breaking from moduli-mediation and anomaly-mediation. The apparent (mirage) unification of soft SUSY breaking terms at Q=mu_mir not associated with any physical threshold is the hallmark of this scenario. The MM-AMSB structure of soft terms arises in models of string compactification with fluxes, where the addition of an anti-brane leads to an uplifting potential and a de Sitter universe, as first constructed by Kachru {\it et al.}. The phenomenology mainly depends on the relative strength of moduli- and anomaly-mediated SUSY breaking contributions, and on the Higgs and matter field modular weights, which are determined by the location of these fields in the extra dimensions. We delineate the allowed parameter space for a low and high value of tan(beta), for a wide range of modular weight choices. We calculate the neutralino relic density and display the WMAP-allowed regions. We show the reach of the CERN LHC and of the International Linear Collider. We discuss aspects of MM-AMSB models for Tevatron, LHC and ILC searches, muon g-2 and b->s \gamma branching fraction. We also calculate direct and indirect dark matter detection rates, and show that almost all WMAP-allowed models should be accessible to a ton-scale noble gas detector. Finally, we comment on the potential of colliders to measure the mirage unification scale and modular weights in the difficult case where mu_mir>>M_GUT.Comment: 34 pages plus 42 EPS figures; version with high resolution figures is at http://www.hep.fsu.edu/~bae

Elucidation of the role of fructose 2,6-bisphosphate in the regulation of glucose fluxes in mice using in vivo (13)C NMR measurements of hepatic carbohydrate metabolism

Fructose 2,6-bisphosphate (Fru-2,6-P2) plays an important role in the regulation of major carbohydrate fluxes as both allosteric activator and inhibitor of target enzymes. To examine the role of Fru-2,6-P2 in the regulation of hepatic carbohydrate metabolism in vivo, Fru-2,6-P2 levels were elevated in ADM mice with adenovirus-mediated overexpression of a double mutant bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (n = 6), in comparison to normal control mice (control, n = 6). The rates of hepatic glycogen synthesis in the ADM and control mouse liver in vivo were measured using new advances in 13C NMR including 3D localization in conjunction with [1-13C]glucose infusion. In addition to glycogen C1, the C6 and C2-C5 signals were measured simultaneously for the first time in vivo, which provide the basis for the estimation of direct and indirect synthesis of glycogen in the liver. The rate of label incorporation into glycogen C1 was not different between the control and ADM group, whereas the rate of label incorporation into glycogen C6 signals was in the ADM group 5.6 +/- 0.5 micro mol.g-1.h-1, which was higher than that of the control group of 3.7 +/- 0.5 micro mol.g-1.h-1 (P < 0.02). The rates of net glycogen synthesis, determined by the glycogen C2-C5 signal changes, were twofold higher in the ADM group (P = 0.04). The results provide direct in vivo evidence that the effects of elevated Fru-2,6-P2 levels in the liver include increased glycogen storage through indirect synthesis of glycogen. These observations provide a key to understanding the mechanisms by which elevated hepatic Fru-2,6-P2 levels promote reduced hepatic glucose production and lower blood glucose in diabetes mellitus