Inhibition of cAMP/PKA Pathway Protects Optic Nerve Head Astrocytes against Oxidative Stress by Akt/Bax Phosphorylation-Mediated Mfn1/2 Oligomerization.

Glaucoma is characterized by a progressive optic nerve degeneration and retinal ganglion cell loss, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role in glaucomatous neurodegeneration. Here, we investigate the impact of activation of cyclic adenosine 3',5'-monophosphate (cAMP)/protein kinase A (PKA) pathway on mitochondrial dynamics of ONH astrocytes exposed to oxidative stress. ONH astrocytes showed a significant loss of astrocytic processes in the glial lamina of glaucomatous DBA/2J mice, accompanied by basement membrane thickening and collagen deposition in blood vessels and axonal degeneration. Serial block-face scanning electron microscopy data analysis demonstrated that numbers of total and branched mitochondria were significantly increased in ONH astrocytes, while mitochondrial length and volume density were significantly decreased. We found that hydrogen peroxide- (H2O2-) induced oxidative stress compromised not only mitochondrial bioenergetics by reducing the basal and maximal respiration but also balance of mitochondrial dynamics by decreasing dynamin-related protein 1 (Drp1) protein expression in rat ONH astrocytes. In contrast, elevated cAMP by dibutyryl-cAMP (dbcAMP) or isobutylmethylxanthine treatment significantly increased Drp1 protein expression in ONH astrocytes. Elevated cAMP exacerbated the impairment of mitochondrial dynamics and reduction of cell viability to oxidative stress in ONH astrocytes by decreasing optic atrophy type 1 (OPA1), and mitofusin (Mfn)1/2 protein expression. Following combined treatment with H2O2 and dbcAMP, PKA inhibition restored mitochondrial dynamics by increasing mitochondrial length and decreasing mitochondrial number, and this promoted cell viability in ONH astrocytes. Also, PKA inhibition significantly promoted Akt/Bax phosphorylation and Mfn1/2 oligomerization in ONH astrocytes. These results suggest that modulation of the cAMP/PKA signaling pathway may have therapeutic potential by activating Akt/Bax phosphorylation and promoting Mfn1/2 oligomerization in glaucomatous ONH astrocytes

Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes.

Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing AKT phosphorylation against oxidative stress. These results strongly indicate that activation of cAMP/PKA pathway has an important role in astrocyte dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic potential for glaucomatous ONH degeneration

Understanding visual map formation through vortex dynamics of spin Hamiltonian models

The pattern formation in orientation and ocular dominance columns is one of the most investigated problems in the brain. From a known cortical structure, we build spin-like Hamiltonian models with long-range interactions of the Mexican hat type. These Hamiltonian models allow a coherent interpretation of the diverse phenomena in the visual map formation with the help of relaxation dynamics of spin systems. In particular, we explain various phenomena of self-organization in orientation and ocular dominance map formation including the pinwheel annihilation and its dependency on the columnar wave vector and boundary conditions.Comment: 4 pages, 15 figure

Nanometer sized Ni-dot/Ag/Pt structure for high reflectance of p-type contact metal in InGaN light emitting diodes

The Ni-dot/Ag/Pt layer, where Ni-dot layer is formed of nanometer sized Ni dots, has been used to improve the reflectivity from the surface of p-type GaN in a light emitting diode (LED). Comparing with Ni/Ag/Pt layer, where Ni layer is a thin film, the Ni-dot/Ag/Pt structure shows significantly improved reflectivity with stable contact resistivity. The optical output power and external quantum efficiency of InGaN LEDs with Ni-dot/Ag/Pt structure for p-metal have improved by 28% and 29%, respectively, over the results of Ni/Ag/Pt structure

Comparison of the performance of photonic band-edge liquid crystal lasers using different dyes as the gain medium

The primary concern of this work is to study the emission characteristics of a series of chiral nematic liquid crystal lasers doped with different laser dyes (DCM, pyrromethene 580, and pyrromethene 597) at varying concentrations by weight (0.5-2 wt %) when optically pumped at 532 nm. Long-wavelength photonic band-edge laser emission is characterized in terms of threshold energy and slope efficiency. At every dye concentration investigated, the pyrromethene 597-doped lasers exhibit the highest slope efficiency (ranging from 15% to 32%) and the DCM-doped lasers the lowest (ranging from 5% to 13%). Similarly, the threshold was found to be, in general, higher for the DCM-doped laser samples in comparison to the pyrromethene-doped laser samples. These results are then compared with the spectral properties, quantum efficiencies and, where possible, fluorescence lifetimes of the dyes dispersed in a common nematic host. In accordance with the low thresholds and high slope efficiencies, the results show that the molar extinction coefficients and quantum efficiencies are considerably larger for the pyrromethene dyes in comparison to DCM, when dispersed in the liquid crystal host.open191

Searching for Exoplanets Using a Microresonator Astrocomb

Detection of weak radial velocity shifts of host stars induced by orbiting planets is an important technique for discovering and characterizing planets beyond our solar system. Optical frequency combs enable calibration of stellar radial velocity shifts at levels required for detection of Earth analogs. A new chip-based device, the Kerr soliton microcomb, has properties ideal for ubiquitous application outside the lab and even in future space-borne instruments. Moreover, microcomb spectra are ideally suited for astronomical spectrograph calibration and eliminate filtering steps required by conventional mode-locked-laser frequency combs. Here, for the calibration of astronomical spectrographs, we demonstrate an atomic/molecular line-referenced, near-infrared soliton microcomb. Efforts to search for the known exoplanet HD 187123b were conducted at the Keck-II telescope as a first in-the-field demonstration of microcombs

Viperin mutation is linked to immunity, immune cell dynamics, and metabolic alteration during VHSV infection in zebrafish

Viperin is a prominent antiviral protein found in animals. The primary function of Viperin is the production of 3’-deoxy-3’,4’-didehydro-cytidine triphosphate (ddhCTP), an inhibitory nucleotide involved in viral RNA synthesis. Studies in mammalian models have suggested that ddhCTP interferes with metabolic proteins. However, this hypothesis has yet to be tested in teleost. In this study, the role of Viperin in regulating metabolic alterations during viral hemorrhagic septicemia virus (VHSV) infection was tested. When infected with VHSV, viperin-/- fish showed considerably higher mortality rates. VHSV copy number and the expression of the NP gene were significantly increased in viperin-/- fish. Metabolic gene analysis revealed significant differences in soda, hif1a, fasn, and acc expression, indicating their impact on metabolism. Cholesterol analysis in zebrafish larvae during VHSV infection showed significant upregulation of cholesterol production without Viperin. In vitro analysis of ZF4 cells suggested a considerable reduction in lipid production and a significant upregulation of reactive oxygen species (ROS) generation with the overexpression of viperin. Neutrophil and macrophage recruitment were significantly modulated in viperin-/- fish compared to the wild-type (WT) fish. Thus, we have demonstrated that Viperin plays a role in interfering with metabolic alterations during VHSV infection

An Integrated-Photonics Optical-Frequency Synthesizer

Integrated-photonics microchips now enable a range of advanced functionalities for high-coherence applications such as data transmission, highly optimized physical sensors, and harnessing quantum states, but with cost, efficiency, and portability much beyond tabletop experiments. Through high-volume semiconductor processing built around advanced materials there exists an opportunity for integrated devices to impact applications cutting across disciplines of basic science and technology. Here we show how to synthesize the absolute frequency of a lightwave signal, using integrated photonics to implement lasers, system interconnects, and nonlinear frequency comb generation. The laser frequency output of our synthesizer is programmed by a microwave clock across 4 THz near 1550 nm with 1 Hz resolution and traceability to the SI second. This is accomplished with a heterogeneously integrated III/V-Si tunable laser, which is guided by dual dissipative-Kerr-soliton frequency combs fabricated on silicon chips. Through out-of-loop measurements of the phase-coherent, microwave-to-optical link, we verify that the fractional-frequency instability of the integrated photonics synthesizer matches the $7.0*10^{-13}$ reference-clock instability for a 1 second acquisition, and constrain any synthesis error to $7.7*10^{-15}$ while stepping the synthesizer across the telecommunication C band. Any application of an optical frequency source would be enabled by the precision optical synthesis presented here. Building on the ubiquitous capability in the microwave domain, our results demonstrate a first path to synthesis with integrated photonics, leveraging low-cost, low-power, and compact features that will be critical for its widespread use.Comment: 10 pages, 6 figure

NCAM (CD56) Expression in keratin-producing odontogenic cysts: aberrant expression in KCOT

Background: Keratin-producing odontogenic cysts (KPOCs) are a group of cystic lesions that are often aggressive, with high rates of recurrence and multifocality. KPOCs included orthokeratinised odontogenic cyst (OOC) and parakeratotic odontogenic cysts, which are now considered true tumours denominated keratocystic odontogenic tumours (KCOTs). GLUT1 is a protein transporter that is involved in the active uptake of glucose across cell membranes and that is overexpressed in tumours in close correlation with the proliferation rate and positron emission tomography (PET) imaging results. Methods: A series of 58 keratin-producing odontogenic cysts was evaluated histologically and immunohistochemically in terms of GLUT1 expression. Different data were correlated using the beta regression model in relation to histological type and immunohistochemical expression of GLUT1, which was quantified using two different morphological methods. Results: KPOC cases comprised 12 OOCs and 46 KCOTs, the latter corresponding to 6 syndromic and 40 sporadic KCOTs. GLUT1 expression was very low in OOC cases compared with KCOT cases, with statistical significant differences when quantification was considered. Different GLUT1 localisation patterns were revealed by immunostaining, with the parabasal cells showing higher reactivity in KCOTs. However, among KCOTs cases, GLUT1 expression was unable to establish differences between syndromic and sporadic cases. Conclusions: GLUT1 expression differentiated between OOC and KCOT cases, with significantly higher expression in KCOTs, but did not differentiate between syndromic and sporadic KCOT cases. However, given the structural characteristics of KCOTs, we hypothesised that PET imaging methodology is probably not a useful diagnostic tool for KCOTs. Further studies of GLUT1 expression and PET examination in KCOT series are needed to confirm this last hypothesis. Keywords: Glucose transporter protein, Immunohistochemistry, Keratin-producing odontogenic cyst, Keratocystic odontogenic tumour, Orthokeratinised odontogenic cyst, Positron emission tomograph