Calcium-sensitive particulate guanylyl cyclase as a modulator of cAMP in olfactory receptor neurons

Journal ArticleThe second messengers cAMP and inositol-1,4,5-triphosphate have been implicated in olfaction in various species. The odorant-induced cGMP response was investigated using cilia preparations and olfactory primary cultures. Odorants cause a delayed and sustained elevation of cGMP. A component of this cGMP response is attributable to the activation of one of two kinetically distinct cilial receptor guanylyl cyclases by calcium and a guanylyl cyclase-activating protein (GCAP). cGMP thus formed serves to augment the cAMP signal in a cGMP-dependent protein kinase (PKG) manner by direct activation of adenylate cyclase. cAMP, in turn, activates cAMP-dependent protein kinase (PKA) to negatively regulate guanylyl cyclase, limiting the cGMP signal. These data demonstrate the existence of a regulatory loop in which cGMP can augment a cAMP signal, and in turn cAMP negatively regulates cGMP production via PKA. Thus, a small, localized, odorant-induced cAMP response may be amplified to modulate downstream transduction enzymes or transcriptional events

Characterization of human GRK7 as a potential cone opsin kinase

Journal ArticlePURPOSE: Homozygous inactivation of the mouse gene for GRK1 (G protein-coupled receptor kinase 1, or rhodopsin kinase) causes severe defects in the recovery of cone phototransduction. However, electroretinographic (ERG) analyses of human oguchi patients with defective GRK1 alleles showed normal or slightly abnormal photopic responses. It remains unclear why the loss of GRK1 yields such different phenotypes in the recovery of mouse and human cones. We examined the localization and enzyme activity of GRK7, the human ortholog of the seventh member of the GRK family, in an attempt to understand its potential role in photopic vision. METHODS: Bioinformatic approaches were used to identify the human GRK7 gene. Human and bovine GRK7 cDNAs were isolated by RT-PCR. Recombinant GRK7, expressed in insect cells, was used to phosphorylate activated rhodopsin. Antibodies raised against GRK7 peptides were used to examine the retina specific expression of GRK7 by immunoblotting and its subcellular localization by immunocytochemistry. RESULTS: The human GRK7 gene is located on chromosome 3q21, spans at least 10 Kb and consists of 4 exons. In human, GRK7 is expressed exclusively in the retina and is found in all retinal neurons, and specifically, in cone outer segments. Recombinant human GRK7 catalyzes rhodopsin phosphorylation in a light dependent manner. We provide evidence that GRK1 and GRK7 are co-expressed in human cones. In contrast, mouse GRK7 is expressed in many tissues including retina where photoreceptors apparently do not express GRK7. CONCLUSIONS: The presence of GRK7 in human, but not in mouse, cone outer segments suggests that GRK7 may function to provide the normal photopic vision reported by oguchi patients with a defective GRK1 gene. The absence of GRK7 expression in cone outer segments of mice is consistent with the notion that mouse cones rely solely on GRK1 to shutoff cone visual pigments

Segmented waveguides in thin silicon-on-insulator

We have developed new silicon-on-insulator waveguide designs for simultaneously achieving both low-loss optical confinement and electrical contacts, and we present a design methodology based on calculating the Bloch modes of such segmented waveguides. With this formalism, waveguides are designed in a single thin layer of silicon-on-insulator to achieve both optical confinement and minimal insertion loss. Waveguides were also fabricated and tested, and the measured data were found to closely agree with theoretical predictions, demonstrating input insertion loss and propagation loss better than 0.1 dB and -16 dB/cm, respectively

On the origin of discrepancies between observed and simulated memory of Arctic Sea ice

To investigate the inherent predictability of sea ice and its representation in climate models, we compare the seasonal-to-interannual memory of Arctic sea ice as given by lagged correlations of sea-ice area anomalies in large model ensembles (Max Planck Institute Grand Ensemble and Coupled Model Intercomparison Project phase 6) and multiple observational products. We find that state-of-the-art climate models significantly overestimate the memory of pan-Arctic sea-ice area from the summer months into the following year. This cannot be explained by internal variability. We further show that the observed summer memory can be disentangled regionally into a reemergence of positive correlations in the perennial ice zone and negative correlations in the seasonal ice zone; the latter giving rise to the discrepancy between observations and model simulations. These findings could explain some of the predictability gap between potential and operational forecast skill of Arctic sea-ice area identified in previous studies

Testrun results from prototype fiber detectors for high rate particle tracking

A fiber detector concept has been realized allowing to registrate particles within less than 100 nsec with a space point precision of about 0.1 mm at low occupancy. Three full size prototypes have been build by different producers and tested at a 3 GeV electron beam at DESY. After 3 m of light guides 8-10 photoelectrons were registrated by multichannel photomultipliers providing an efficiency of more than 99%. Using all available data a resolution of 0.086 mm was measured.Comment: 18 pages, 17 figure

Integrable Discretizations of Chiral Models

A construction of conservation laws for chiral models (generalized sigma-models on a two-dimensional space-time continuum using differential forms is extended in such a way that it also comprises corresponding discrete versions. This is achieved via a deformation of the ordinary differential calculus. In particular, the nonlinear Toda lattice results in this way from the linear (continuum) wave equation. The method is applied to several further examples. We also construct Lax pairs and B\"acklund transformations for the class of models considered in this work.Comment: 14 pages, Late