Nitric oxide-independent vasodilator rescues heme-oxidized soluble guanylate cyclase from proteosomal degradation

Background: Nitric oxide (NO) is an essential vasodilator. In vascular diseases, oxidative stress attenuates NO signaling by both chemical scavenging of free NO and oxidation and down-regulation of its major intracellular receptor, the alpha/beta heterodimeric heme-containing soluble guanylate cyclase (sGC). Oxidation can also induce loss of sGC's heme and responsiveness to NO. Results: sGC activators such as BAY 58-2667 bind to oxidized/heme-free sGC and reactivate the enzyme to exert disease-specific vasodilation. Here we show that oxidation-induced down-regulation of sGC protein extends to isolated blood vessels. Mechanistically, degradation was triggered through sGC ubiquitination and proteasomal degradation. The heme-binding site ligand, BAY 58-2667, prevented sGC ubiquitination and stabilized both alpha and beta subunits. Conclusion: Collectively, our data establish oxidation-ubiquitination of sGC as a modulator of NO/cGMP signaling and point to a new mechanism of action for sGC activating vasodilators by stabilizing their receptor, oxidized/heme-free sGC

Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis

Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics

Coastal greening of grey infrastructure: an update on the state-of-the-art

\ua9 2023 Emerald Publishing Limited: All rights reserved.In the marine environment, greening of grey infrastructure (GGI) is a rapidly growing field that attempts to encourage native marine life to colonize marine artificial structures to enhance biodiversity, thereby promoting ecosystem functioning and hence service provision. By designing multifunctional sea defences, breakwaters, port complexes and off-shore renewable energy installations, these structures can yield myriad environmental benefits, in particular, addressing UN SDG 14: Life below water. Whilst GGI has shown great promise and there is a growing evidence base, there remain many criticisms and knowledge gaps, and some feel that there is scope for GGI to be abused by developers to facilitate harmful development. Given the surge of research in this field in recent years, it is timely to review the literature to provide an update update on the state-of-the-art of the field in relation to the many criticisms and identify remaining knowledge gaps. Despite the rapid and significant advances made in this field, there is currently a lack of science and practice outside of academic sectors in the developed world, and there is a collective need for schemes that encourage intersectoral and transsectoral research, knowledge exchange, and capacity building to optimize GGI in the pursuit of contributing to sustainable development

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fifteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health Contract P01-DC00361National Institutes of Health Contract N01-DC22402National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-94-C-0087U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-93-1-1399U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-94-1-1079U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-92-J-1814National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-88-K-0604National Aeronautics and Space Administration Grant NCC 2-771U.S. Air Force - Office of Scientific Research Grant F49620-94-1-0236U.S. Air Force - Office of Scientific Research Agreement with Brandeis Universit

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on twelve research projects.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Grant 5 R01 DC00126National Institutes of Health Grant R01-DC00270U.S. Air Force - Office of Scientific Research Contract AFOSR-90-0200National Institutes of Health Grant R29-DC00625U.S. Navy - Office of Naval Research Grant N00014-88-K-0604U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-1814U.S. Navy - Naval Training Systems Center Contract N61339-93-M-1213U.S. Navy - Naval Training Systems Center Contract N61339-93-C-0055U.S. Navy - Naval Training Systems Center Contract N61339-93-C-0083U.S. Navy - Office of Naval Research Grant N00014-92-J-4005U.S. Navy - Office of Naval Research Grant N00014-93-1-119

Influence of Bonner sphere response functions above 20 MeV on unfolded neutron spectra and doses.

Monte Carlo (MC) codes for neutron transport calculations such as MCNP, MCNPX, FLUKA, PHITS, and GEANT4, crucially rely on cross sections that describe the interaction of neutrons with nuclei. For neutron energies below 20 MeV, evaluated cross sections are available that are validated against experimental data. In contrast, for high energies (above 20 MeV) experimental data are scarce and, for this reason, every neutron transport code is based on theoretical nuclear models to describe interactions of neutrons with nuclei in matter. Here we report on the calculation of a complete set of response functions for a Bonner spheres spectrometer (BSS), by means of GEANT4 using the Bertini and Binary Intranuclear Cascade (INC) models for energies above 20 MeV. The recent results were compared with those calculated by MCNP/LAHET and MCNP/HADRON MC codes. It turns out that, whatever code used, the response functions were rather similar for neutron energies below 20 MeV, for all 16 detector/moderator combinations of the considered BSS system. For higher energies, however, differences of more than a factor of 2 were observed, depending on neutron energy, detector/moderator combination, MC code, and nuclear model used. These differences are discussed in terms of neutron fluence rates measured at the environmental research station (UFS), “Schneefernerhaus”, (Zugspitze mountain, Germany, 2650 m a.s.l.) for energies below 0.4 eV (thermal neutrons), between 0.4 eV and 100 keV (epithermal neutrons), between 100 keV and 20 MeV (evaporation neutrons), and above 20 MeV (cascade neutrons). In terms of total neutron fluence rates, relative differences of up to 4% were obtained when compared to the standard MCNP/LAHET results, while in terms of total ambient dose equivalent, relative differences of up to 8% were obtained. Both the GEANT4 Binary INC and Bertini INC gave somewhat larger fluence and dose rates in the epithermal region. Most relevant for dose, however, those response functions calculated with the GEANT4 Bertini INC model provided about 18% less neutrons in the cascade region, which led to a roughly 13% smaller contribution of these neutrons to ambient dose equivalent. It is concluded that doses from secondary neutrons from cosmic radiation as deduced from BSS measurements are uncertain by about 10%, simply because of some differences in nuclear models used by various neutron transport codes