Enzymatic Relay Mechanism Stimulates Cyclic GMP Synthesis in Rod Photoresponse: Biochemical and Physiological Study in Guanylyl Cyclase Activating Protein 1 Knockout Mice

Regulation of cGMP synthesis by retinal membrane guanylyl cyclase isozymes (RetGC1 and RetGC2) in rod and cone photoreceptors by calcium-sensitive guanylyl cyclase activating proteins (GCAP1 and GCAP2) is one of the key molecular mechanisms affecting the response to light and is involved in congenital retinal diseases. The objective of this study was to identify the physiological sequence of events underlying RetGC activation in vivo, by studying the electrophysiological and biochemical properties of mouse rods in a new genetic model lacking GCAP1. The GCAP1−/− retinas expressed normal levels of RetGC isozymes and other phototransduction proteins, with the exception of GCAP2, whose expression was elevated in a compensatory fashion. RetGC activity in GCAP1−/− retinas became more sensitive to Ca2+ and slightly increased. The bright flash response in electroretinogram (ERG) recordings recovered quickly in GCAP1−/−, as well as in RetGC1−/−GCAP1−/−, and RetGC2−/−GCAP1−/− hybrid rods, indicating that GCAP2 activates both RetGC isozymes in vivo. Individual GCAP1−/− rod responses varied in size and shape, likely reflecting variable endogenous GCAP2 levels between different cells, but single-photon response (SPR) amplitude and time-to-peak were typically increased, while recovery kinetics remained faster than in wild type. Recovery from bright flashes in GCAP1−/− was prominently biphasic, because rare, aberrant SPRs producing the slower tail component were magnified. These data provide strong physiological evidence that rod photoresponse recovery is shaped by the sequential recruitment of RetGC isozyme activation by GCAPs according to the different GCAP sensitivities for Ca2+ and specificities toward RetGC isozymes. GCAP1 is the ‘first-response’ sensor protein that stimulates RetGC1 early in the response and thus limits the SPR amplitude, followed by activation of GCAP2 that adds stimulation of both RetGC1 and RetGC2 to speed-up photoreceptor recovery

Emission-line Variability during a Nonthermal Outburst in the Gamma-Ray Bright Quasar 1156+295

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.We present multi-epoch optical spectra of the γ-ray bright blazar 1156+295 (4C +29.45, Ton 599) obtained with the 4.3 m Lowell Discovery Telescope. During a multiwavelength outburst in late 2017, when the γ-ray flux increased to 2.5 × 10−6 phot cm−2 s−1 and the quasar was first detected at energies ≥100 GeV, the flux of the Mg ii λ2798 emission line changed, as did that of the Fe emission complex at shorter wavelengths. These emission-line fluxes increased along with the highly polarized optical continuum flux, which is presumably synchrotron radiation from the relativistic jet, with a relative time delay of ≲2 weeks. This implies that the line-emitting clouds lie near the jet, which points almost directly toward the line of sight. The emission-line radiation from such clouds, which are located outside the canonical accretion-disk related broad-line region, may be a primary source of seed photons that are up-scattered to γ-ray energies by relativistic electrons in the jet. © 2022. The Author(s). Published by the American Astronomical Society.This research was supported in part by NASA Fermi guest investigator program grants 80NSSC19K1504 and 80NSSC20K1565. We thank A. Tchekhovskoy for discussion of possible origins of the variable line-emitting clouds. These results made use of the Lowell Discovery Telescope (LDT) at Lowell Observatory. Lowell Observatory is a private, non-profit institution dedicated to astrophysical research and public appreciation of astronomy, and operates the LDT in partnership with Boston University, the University of Maryland, the University of Toledo, Northern Arizona University and Yale University. This study was based in part on observations conducted using the 1.8 m Perkins Telescope Observatory (PTO) in Arizona, which is owned and operated by Boston University. I.A. acknowledges financial support from the Spanish "Ministerio de Ciencia e Innovación" (MCINN) through the "Center of Excellence Severo Ochoa" award for the Instituto de Astrofísica de Andalucía-CSIC (SEV-2017-0709). Acquisition and reduction of the MAPCAT data were supported in part by MICINN through grants AYA2016-80889-P and PID2019-107847RB-C44. The MAPCAT observations were carried out at the German-Spanish Calar Alto Observatory, which is jointly operated by Junta de Andalucía and Consejo Superior de Investigaciones Científicas. Data from the Steward Observatory spectropolarimetric monitoring project were used; this program was supported by Fermi Guest Investigator grants NNX08AW56G, NNX09AU10G, NNX12AO93G, and NNX15AU81G. C.C. acknowledges support from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program under the grant agreement No. 771282.Peer reviewe

Polarized blazar X-rays imply particle acceleration in shocks

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization—the only range available until now—probe extended regions of the jet containing particles that left the acceleration site days to years earlier1,2,3, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree ΠX of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock

X-ray Polarization Observations of BL Lacertae

Blazars are a class of jet-dominated active galactic nuclei with a typical double-humped spectral energy distribution. It is of common consensus the Synchrotron emission to be responsible for the low frequency peak, while the origin of the high frequency hump is still debated. The analysis of X-rays and their polarization can provide a valuable tool to understand the physical mechanisms responsible for the origin of high-energy emission of blazars. We report the first observations of BL Lacertae performed with the Imaging X-ray Polarimetry Explorer ({IXPE}), from which an upper limit to the polarization degree $\Pi_X<$12.6\% was found in the 2-8 keV band. We contemporaneously measured the polarization in radio, infrared, and optical wavelengths. Our multiwavelength polarization analysis disfavors a significant contribution of proton synchrotron radiation to the X-ray emission at these epochs. Instead, it supports a leptonic origin for the X-ray emission in BL Lac.Comment: 17 pages, 5 figures, accepted for publication in ApJ

Search techniques in intelligent classification systems

A unified methodology for categorizing various complex objects is presented in this book. Through probability theory, novel asymptotically minimax criteria suitable for practical applications in imaging and data analysis are examined including the special cases such as the Jensen-Shannon divergence and the probabilistic neural network. An optimal approximate nearest neighbor search algorithm, which allows faster classification of databases is featured. Rough set theory, sequential analysis and granular computing are used to improve performance of the hierarchical classifiers. Practical examples in face identification (including deep neural networks), isolated commands recognition in voice control system and classification of visemes captured by the Kinect depth camera are included. This approach creates fast and accurate search procedures by using exact probability densities of applied dissimilarity measures. This book can be used as a guide for independent study and as supplementary material for a technically oriented graduate course in intelligent systems and data mining. Students and researchers interested in the theoretical and practical aspects of intelligent classification systems will find answers to: - Why conventional implementation of the naive Bayesian approach does not work well in image classification? - How to deal with insufficient performance of hierarchical classification systems? - Is it possible to prevent an exhaustive search of the nearest neighbor in a database