Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

Agile training to help enable standardisation of phytoplankton sampling and gross gill terminology across the Scottish sector

Current aquaculture operations in the UK are dominated by finfish farming in Scotland, contributing over £1.8 billion to the Scottish economy with the ambition to double this value by 2030. Finfish health is the top priority across the sector as healthy fish enjoy higher survival rates. One of the most important threats is the occurrence of gill disease, e.g. due to HABs, with potentially devastating impacts on fish health resulting in mortality, reduced welfare, and associated losses in profit on the rise. To understand this threat better, high-quality data generation for reporting is essential. For example, a significant body of work – catalysed by the Scottish Government’s Farmed Fish Health Framework and involving SAIC, agencies, regulators, and a large representation from producers within the sector – acknowledged the need for procedures for sustained and standardised surveillance and reporting of algal blooms, and a standardised operating procedure was developed. The sector representatives are unanimous in the need for developing specific skills to operate under the HABs SOP and in fish health generally. Two courses have been funded by Defra, UK, in the area of aquaculture operators’ skills development. The first course aims for standardisation of HABs sampling and classification, and understanding of the data and modelling associated with mitigation and management of HABs events, and will be delivered through a partnership between SAIC, the Scottish Association for Marine Science (SAMS) and Lantra. The second course is under the health framework and aims to improve the skills and knowledge of technicians and veterinary professionals currently working in, or interested in diversifying into, the seafood sector. An initial aim of the latter course, a partnership between SRUC and SSF, is to standardise salmon gross gill health monitoring terminology

Agile training to help enable standardisation of phytoplankton sampling and gross gill terminology across the Scottish sector

Current aquaculture operations in the UK are dominated by finfish farming in Scotland, contributing over £1.8 billion to the Scottish economy with the ambition to double this value by 2030. Finfish health is the top priority across the sector as healthy fish enjoy higher survival rates. One of the most important threats is the occurrence of gill disease, e.g. due to HABs, with potentially devastating impacts on fish health resulting in mortality, reduced welfare, and associated losses in profit on the rise. To understand this threat better, high-quality data generation for reporting is essential. For example, a significant body of work – catalysed by the Scottish Government’s Farmed Fish Health Framework and involving SAIC, agencies, regulators, and a large representation from producers within the sector – acknowledged the need for procedures for sustained and standardised surveillance and reporting of algal blooms, and a standardised operating procedure was developed. The sector representatives are unanimous in the need for developing specific skills to operate under the HABs SOP and in fish health generally. Two courses have been funded by Defra, UK, in the area of aquaculture operators’ skills development. The first course aims for standardisation of HABs sampling and classification, and understanding of the data and modelling associated with mitigation and management of HABs events, and will be delivered through a partnership between SAIC, the Scottish Association for Marine Science (SAMS) and Lantra. The second course is under the health framework and aims to improve the skills and knowledge of technicians and veterinary professionals currently working in, or interested in diversifying into, the seafood sector. An initial aim of the latter course, a partnership between SRUC and SSF, is to standardise salmon gross gill health monitoring terminology

Agile training to help enable standardisation of phytoplankton sampling and gross gill terminology across the Scottish sector

Current aquaculture operations in the UK are dominated by finfish farming in Scotland, contributing over £1.8 billion to the Scottish economy with the ambition to double this value by 2030. Finfish health is the top priority across the sector as healthy fish enjoy higher survival rates. One of the most important threats is the occurrence of gill disease, e.g. due to HABs, with potentially devastating impacts on fish health resulting in mortality, reduced welfare, and associated losses in profit on the rise. To understand this threat better, high-quality data generation for reporting is essential. For example, a significant body of work – catalysed by the Scottish Government’s Farmed Fish Health Framework and involving SAIC, agencies, regulators, and a large representation from producers within the sector – acknowledged the need for procedures for sustained and standardised surveillance and reporting of algal blooms, and a standardised operating procedure was developed. The sector representatives are unanimous in the need for developing specific skills to operate under the HABs SOP and in fish health generally. Two courses have been funded by Defra, UK, in the area of aquaculture operators’ skills development. The first course aims for standardisation of HABs sampling and classification, and understanding of the data and modelling associated with mitigation and management of HABs events, and will be delivered through a partnership between SAIC, the Scottish Association for Marine Science (SAMS) and Lantra. The second course is under the health framework and aims to improve the skills and knowledge of technicians and veterinary professionals currently working in, or interested in diversifying into, the seafood sector. An initial aim of the latter course, a partnership between SRUC and SSF, is to standardise salmon gross gill health monitoring terminology

Fermi Gamma-ray Imaging of a Radio Galaxy

The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating from the giant radio lobes of the radio galaxy Centaurus A. The resolved gamma-ray image shows the lobes clearly separated from the central active source. In contrast to all other active galaxies detected so far in high-energy gamma-rays, the lobe flux constitutes a considerable portion (>1/2) of the total source emission. The gamma-ray emission from the lobes is interpreted as inverse Compton scattered relic radiation from the cosmic microwave background (CMB), with additional contribution at higher energies from the infrared-to-optical extragalactic background light (EBL). These measurements provide gamma-ray constraints on the magnetic field and particle energy content in radio galaxy lobes, and a promising method to probe the cosmic relic photon fields.Comment: 27 pages, includes Supplementary Online Material; corresponding authors: C.C. Cheung, Y. Fukazawa, J. Knodlseder, L. Stawar

Detection of Gamma-Ray Emission from the Starburst Galaxies M82 and NGC 253 with the Large Area Telescope on Fermi

We report the detection of high-energy gamma-ray emission from two starburst galaxies using data obtained with the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. Steady point-like emission above 200 MeV has been detected at significance levels of 6.8 sigma and 4.8 sigma respectively, from sources positionally coincident with locations of the starburst galaxies M82 and NGC 253. The total fluxes of the sources are consistent with gamma-ray emission originating from the interaction of cosmic rays with local interstellar gas and radiation fields and constitute evidence for a link between massive star formation and gamma-ray emission in star-forming galaxies.Comment: Submitted to ApJ Letter

Defining hereditary alpha-tryptasemia as a risk/modifying factor for anaphylaxis: are we there yet?

Hereditary a-tryptasemia (HaT) is a common autosomal dominant genet-ic trait with variable penetrance associated with increased serum baseline tryptase (SBT) levels. Clinical manifestations may range from an absence of symptoms to overtly severe and recurrent anaphylaxis. Symptoms have been claimed to result from excessive activation of EGF-like module -con-taining mucin-like hormone receptor-like 2 (EMR2) and protease activat-ed receptor 2 (PAR-2) receptors by a/13-tryptase heterotetramers. Herein, we aimed to review the evidence on whether HaT can be considered a hereditary risk factor or a modifying factor for anaphylaxis. Increased SBT levels have been linked to an increased risk of anaphylaxis. Likewise, recent studies have shown that HaT might be associated with a higher risk of developing anaphylaxis and more severe anaphylaxis. The same has also been shown for patients with clonal mast cell disorders, in whom the co-existence of HaT might lead to a greater propensity for se-vere, potentially life-threatening anaphylaxis. However, studies leading to such conclusions are generally limited in sample size, while other studies have shown opposing results. As such, further studies investigating the po-tential association of HaT with anaphylaxis caused by different triggers, and different severity grades, in both patients with clonal mast cell activa-tion syndromes and the general population are still needed

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Search for gamma-ray emission from magnetars with the Fermi Large Area Telescope

We report on the search for 0.1-10 GeV emission from magnetars in 17 months of Fermi Large Area Telescope (LAT) observations. No significant evidence for gamma-ray emission from any of the currently-known magnetars is found. The most stringent upper limits to date on their persistent emission in the Fermi-LAT energy range are estimated between ~10^{-12}-10^{-10} erg/s/cm2, depending on the source. We also searched for gamma-ray pulsations and possible outbursts, also with no significant detection. The upper limits derived support the presence of a cut-off at an energy below a few MeV in the persistent emission of magnetars. They also show the likely need for a revision of current models of outer gap emission from strongly magnetized pulsars, which, in some realizations, predict detectable GeV emission from magnetars at flux levels exceeding the upper limits identified here using the Fermi-LAT observations.Comment: ApJ Letters in press; Corresponding authors: Caliandro G. A., Hadasch D., Rea N., Burnett