Rhythmic regulation of photoreceptor and RPE genes important for vision and genetically associated with severe retinal diseases

Purpose: The aim of the present study was to identify candidate genes for mediating daily adjustment of vision. Methods: Genes important for vision and genetically associated with severe retinal diseases were tested for 24-hour rhythms in transcript levels in neuronal retina, microdissected photoreceptors, photoreceptor-related pinealocytes, and retinal pigment epithelium-choroid (RPE-choroid) complex by using quantitative PCR. Results: Photoreceptors of wildtype mice display circadian clock-dependent regulation of visual arrestins (Arr1, Arr4) and the visual cycle gene Rdh12, whereas cells of the RPE-choroid exhibit light-dependent regulation of the visual cycle key genes Lrat, Rpe65, and Rdh5. Clock-driven rhythmicity of Arr1, Arr4, and Rdh12 was observed also in rat pinealocytes, to persist in a mouse model of diabetic retinopathy (db/db) and, in the case of Arr1, to be abolished in retinae of mice deficient for dopamine D4 receptors. Therefore, the expression rhythms appear to be evolutionary conserved, to be unaffected in diabetic retinopathy, and, for Arr1, to require dopamine signaling via dopamine D4 receptors. Conclusions: The data of the present study suggest that daily adjustment of retinal function combines clock dependent regulation of genes responsible for phototransduction termination (Arr1, Arr4) and detoxification (Rdh12) in photoreceptors with light-dependent regulation of genes responsible for retinoid recycling (Lrat, Rpe65, and Rdh5) in RPE. Furthermore, they indicate circadian and light dependent regulation of genes genetically associated with severe retinal diseases

Dust in the bright supernova remnant N49 in the LMC

We investigate the dust associated with the supernova remnant (SNR) N49 in the Large Magellanic Cloud (LMC) as observed with the Herschel Space Observatory. N49 is unusually bright because of an interaction with a molecular cloud along its eastern edge. We have used PACS and SPIRE to measure the far IR flux densities of the entire SNR and of a bright region on the eastern edge of the SNR where the SNR shock is encountering the molecular cloud. Using these fluxes supplemented with archival data at shorter wavelengths, we estimate the dust mass associated with N49 to be about 10 Msun. The bulk of the dust in our simple two-component model has a temperature of 20-30 K, similar to that of nearby molecular clouds. Unfortunately, as a result of the limited angular resolution of Herschel at the wavelengths sampled with SPIRE, the uncertainties are fairly large. Assuming this estimate of the dust mass associated with the SNR is approximately correct, it is probable that most of the dust in the SNR arises from regions where the shock speed is too low to produce significant X-ray emission. The total amount of warm 50-60 K dust is ~0.1 or 0.4 Msun, depending on whether the dust is modeled in terms of carbonaceous or silicate grains. This provides a firm lower limit to the amount of shock heated dust in N49.Comment: accepted by the Astronomy & Astrophysics Lette

Six Years of Chandra Observations of Supernova Remnants

We present a review of the first six years of Chandra X-ray Observatory observations of supernova remnants. From the official "first-light" observation of Cassiopeia A that revealed for the first time the compact remnant of the explosion, to the recent million-second spectrally-resolved observation that revealed new details of the stellar composition and dynamics of the original explosion, Chandra observations have provided new insights into the supernova phenomenon. We present an admittedly biased overview of six years of these observations, highlighting new discoveries made possible by Chandra's unique capabilities.Comment: 82 pages, 28 figures, for the book Astrophysics Update

Meissner Effect and Vortex Dynamics in Quark Stars -- A Model for Soft Gamma-Ray Repeaters

We present a new model for soft gamma-ray repeaters based on a quark star born with temperatures above the critical value (T_c) for the onset of the colour-flavor locked superconductivity. The quark star then quickly cools below T_c, expelling a fraction of the surface magnetic field via the Meissner effect. We show that if a small fraction (\leq 10%) of the surface magnetic field (10^{14} - 10^{15} {\rm G}) is expelled, it quickly decays via magnetic reconnection and heats up the quark star surface to temperatures > 10^9 {\rm K}. Created (e^{+},e^{-}) pairs annihilate into gamma rays emitted in a giant burst (the first burst in our model), with a luminosity of \sim 10^{45} {\rm ergs} {\rm s}^{-1}. Subsequent bursts result from the restructuring of the surface magnetic field following the formation and relaxation of a vortex lattice which confines the internal magnetic field. During this phase, energy is sporadically released as a consequence of magnetic reconnection events in the entangled surface magnetic field as it evolves into a smooth, more stable, configuration. The star eventually enters a quiescent phase in which energy is continuously supplied by vortex annihilation at the surface. As the star spins down, the outermost vortex lines will be pushed to the surface where they annihilate and release their confined magnetic field. We show that the corresponding luminosity is L_v \sim 10^{36} {\rm ergs} {\rm s}^{-1} for a typical soft gamma-ray repeater spinning with a period of 8 {\rm s} and a surface magnetic field not exceeding 10^{15} {\rm G}. Our model can be applied to any situation where a T>T_{\rm c} quark star is generated. We discuss the connection between anomalous X-ray pulsars and soft gamma-ray repeaters in the context of our model.Comment: Version to appear in A&A. Added an entire section (section 8) discussing among other points, the AXP-SGR connection, glitches and the issue of transverse velocities in our model. References have been updated accordingly. (9 pages, 5 figures

Thiopurine Methyltransferase Predicts the Extent of Cytotoxicty and DNA Damage in Astroglial Cells after Thioguanine Exposure

Thiopurine methyltransferase (Tpmt) is the primary enzyme responsible for deactivating thiopurine drugs. Thiopurine drugs (i.e., thioguanine [TG], mercaptopurine, azathioprine) are commonly used for the treatment of cancer, organ transplant, and autoimmune disorders. Chronic thiopurine therapy has been linked to the development of brain cancer (most commonly astrocytomas), and Tpmt status has been associated with this risk. Therefore, we investigated whether the level of Tpmt protein activity could predict TG-associated cytotoxicity and DNA damage in astrocytic cells. We found that TG induced cytotoxicity in a dose-dependent manner in Tpmt+/+, Tpmt+/− and Tpmt−/− primary mouse astrocytes and that a low Tpmt phenotype predicted significantly higher sensitivity to TG than did a high Tpmt phenotype. We also found that TG exposure induced significantly more DNA damage in the form of single strand breaks (SSBs) and double strand breaks (DSBs) in primary astrocytes with low Tpmt versus high Tpmt. More interestingly, we found that Tpmt+/− astrocytes had the highest degree of cytotoxicity and genotoxicity (i.e., IC50, SSBs and DSBs) after TG exposure. We then used human glioma cell lines as model astroglial cells to represent high (T98) and low (A172) Tpmt expressers and found that A172 had the highest degree of cytoxicity and SSBs after TG exposure. When we over-expressed Tpmt in the A172 cell line, we found that TG IC50 was significantly higher and SSB's were significantly lower as compared to mock transfected cells. This study shows that low Tpmt can lead to greater sensitivity to thiopurine therapy in astroglial cells. When Tpmt deactivation at the germ-line is considered, this study also suggests that heterozygosity may be subject to the greatest genotoxic effects of thiopurine therapy

Comparative Metaproteomic Analysis on Consecutively Rehmannia glutinosa-Monocultured Rhizosphere Soil

National Natural Science Foundation of China [30772729, 30671220, 31070403]; Natural Science Foundation of Fujian province, China [2008J0051]Background: The consecutive monoculture for most of medicinal plants, such as Rehmannia glutinosa, results in a significant reduction in the yield and quality. There is an urgent need to study for the sustainable development of Chinese herbaceous medicine. Methodology/Principal Findings: Comparative metaproteomics of rhizosphere soil was developed and used to analyze the underlying mechanism of the consecutive monoculture problems of R. glutinosa. The 2D-gel patterns of protein spots for the soil samples showed a strong matrix dependency. Among the spots, 103 spots with high resolution and repeatability were randomly selected and successfully identified by MALDI TOF-TOF MS for a rhizosphere soil metaproteomic profile analysis. These proteins originating from plants and microorganisms play important roles in nutrient cycles and energy flow in rhizospheric soil ecosystem. They function in protein, nucleotide and secondary metabolisms, signal transduction and resistance. Comparative metaproteomics analysis revealed 33 differentially expressed protein spots in rhizosphere soil in response to increasing years of monoculture. Among them, plant proteins related to carbon and nitrogen metabolism and stress response, were mostly up-regulated except a down-regulated protein (glutathione S-transferase) involving detoxification. The phenylalanine ammonia-lyase was believed to participate in the phenylpropanoid metabolism as shown with a considerable increase in total phenolic acid content with increasing years of monoculture. Microbial proteins related to protein metabolism and cell wall biosynthesis, were up-regulated except a down-regulated protein (geranylgeranyl pyrophosphate synthase) functioning in diterpenoid synthesis. The results suggest that the consecutive monoculture of R. glutinosa changes the soil microbial ecology due to the exudates accumulation, as a result, the nutrient cycles are affected, leading to the retardation of plant growth and development. Conclusions/Significance: Our results demonstrated the interactions among plant, soil and microflora in the proteomic level are crucial for the productivity and quality of R. glutinosa in consecutive monoculture system