The P2Y12 receptor induces platelet aggregation through weak activation of the αIIbβ3 integrin – a phosphoinositide 3-kinase-dependent mechanism

AbstractHigh concentrations of adenosine-5′-diphosphate ADP are able to induce partial aggregation without shape change of P2Y1 receptor-deficient mouse platelets through activation of the P2Y12 receptor. In the present work we studied the transduction pathways selectively involved in this phenomenon. Flow cytometric analyses using R-phycoerythrin-conjugated JON/A antibody (JON/A-PE), an antibody which recognizes activated mouse αIIbβ3 integrin, revealed a low level activation of αIIbβ3 in P2Y1 receptor-deficient platelets in response to 100 μM ADP or 1 μM 2MeS-ADP. Adrenaline induced no such activation but strongly potentiated the effect of ADP in a dose-dependent manner. Global phosphorylation of 32P-labeled platelets showed that P2Y12-mediated aggregation was not accompanied by an increase in the phosphorylation of myosin light chain (P20) or pleckstrin (P47) and was not affected by the protein kinase C (PKC) inhibitor staurosporine. On the other hand, two unrelated phosphoinositide 3-kinase inhibitors, wortmannin and LY294002, inhibited this aggregation. Our results indicate that (i) the P2Y12 receptor is able to trigger a P2Y1 receptor-independent inside-out signal leading to αIIbβ3 integrin activation and platelet aggregation, (ii) ADP and adrenaline use different signaling pathways which synergize to activate the αIIbβ3 integrin, and (iii) the transduction pathway triggered by the P2Y12 receptor is independent of PKC but dependent on phosphoinositide 3-kinase

Do electron-capture supernovae make neutron stars? First multidimensional hydrodynamic simulations of the oxygen deflagration

Context. In the classical picture, electron-capture supernovae and the accretion-induced collapse of oxygen-neon white dwarfs undergo an oxygen deflagration phase before gravitational collapse produces a neutron star. These types of core collapse events are postulated to explain several astronomical phenomena. In this work, the oxygen deflagration phase is simulated for the first time using multidimensional hydrodynamics. Aims. By simulating the oxygen deflagration with multidimensional hydrodynamics and a level-set-based flame approach, new insights can be gained into the explosive deaths of 8−10 M⊙ stars and oxygen-neon white dwarfs that accrete material from a binary companion star. The main aim is to determine whether these events are thermonuclear or core-collapse supernova explosions, and hence whether neutron stars are formed by such phenomena. Methods. The oxygen deflagration is simulated in oxygen-neon cores with three different central ignition densities. The intermediate density case is perhaps the most realistic, being based on recent nuclear physics calculations and 1D stellar models. The 3D hydrodynamic simulations presented in this work begin from a centrally confined flame structure using a level-set-based flame approach and are performed in 2563 and 5123 numerical resolutions. Results. In the simulations with intermediate and low ignition density, the cores do not appear to collapse into neutron stars. Instead, almost a solar mass of material becomes unbound from the cores, leaving bound remnants. These simulations represent the case in which semiconvective mixing during the electron-capture phase preceding the deflagration is inefficient. The masses of the bound remnants double when Coulomb corrections are included in the equation of state, however they still do not exceed the effective Chandrasekhar mass and, hence, would not collapse into neutron stars. The simulations with the highest ignition density (log 10ρc = 10.3), representing the case where semiconvective mixing is very efficient, show clear signs that the core will collapse into a neutron star

Bipolar planetary nebulae from common envelope evolution of binary stars

Asymmetric shapes and evidence for binary central stars suggest a common-envelope origin for many bipolar planetary nebulae. The bipolar components of the nebulae are observed to expand faster than the rest and the more slowly expanding material has been associated with the bulk of the envelope ejected during the common-envelope phase of a stellar binary system. Common-envelope evolution in general remains one of the biggest uncertainties in binary star evolution and the origin of the fast outflow has not been explained satisfactorily. We perform three-dimensional magnetohydrodynamic simulations of common-envelope interaction with the moving-mesh code AREPO. Starting from the plunge-in of the companion into the envelope of an asymptotic giant branch star and covering hundreds of orbits of the binary star system, we are able to follow the evolution to complete envelope ejection. We find that magnetic fields are strongly amplified in two consecutive episodes. First, when the companion spirals in the envelope and, second, when it forms a contact binary with the core of the former giant star. In the second episode, a magnetically-driven, high-velocity outflow of gas is launched self-consistently in our simulations. The outflow is bipolar and the gas is additionally collimated by the ejected common envelope. The resulting structure reproduces typical morphologies and velocities observed in young planetary nebulae. We propose that the magnetic driving mechanism is a universal consequence of common envelope interaction responsible for a substantial fraction of observed planetary nebulae. Such a mechanism likely also exists in the common-envelope phase of other binary stars that lead to the formation of Type Ia supernovae, X-ray binaries and gravitational-wave merger events.Comment: 9 pages, 11 figures; accepted for publication by A&

Lentiviral RNAs can use different mechanisms for translation initiation

Abstract The full-length genomic RNA of lentiviruses can be translated to produce proteins and incorporated as genomic RNA in the viral particle. Interestingly, both functions are driven by the genomic 5 -UTR (5 -untranslated region), which harbours structural RNA motifs for the replication cycle of the virus. Recent work has shown that this RNA architecture also functions as an IRES (internal ribosome entry site) in HIV-1 and -2, and in SIV (simian immunodeficiency virus). In addition, the IRES extends to the gag coding region for all these viruses and this leads to the synthesis of shorter isoforms of the Gag polyprotein from downstream initiation codons. In the present study, we have investigated how different members of the lentivirus family (namely HIV-1 and -2, and SIV) can initiate protein synthesis by distinct mechanisms. For this, we have used the competitive reticulocyte lysate that we have recently described. Our results show that HIV-1 is able to drive the synthesis of the Gag polyprotein both by a classical cap-dependent mechanism and an IRES, whereas HIV-2 and SIV appear to use exclusively an IRES mechanism

The 5′-untranslated region of the mouse mammary tumor virus mRNA exhibits cap-independent translation initiation

In this study, we demonstrate the identification of an internal ribosome entry site (IRES) within the 5′-untranslated region (5′-UTR) of the mouse mammary tumor virus (MMTV). The 5′-UTR of the full-length mRNA derived from the infectious, complete MMTV genome was cloned into a dual luciferase reporter construct containing an upstream Renilla luciferase gene (RLuc) and a downstream firefly luciferase gene (FLuc). In rabbit reticulocyte lysate, the MMTV 5′-UTR was capable of driving translation of the second cistron. In vitro translational activity from the MMTV 5′-UTR was resistant to the addition of m7GpppG cap-analog and cleavage of eIF4G by foot-and-mouth disease virus (FMDV) L-protease. IRES activity was also demonstrated in the Xenopus laevis oocyte by micro-injection of capped and polyadenylated bicistronic RNAs harboring the MMTV-5′-UTR. Finally, transfection assays showed that the MMTV-IRES exhibits cell type-dependent translational activity, suggesting a requirement for as yet unidentified cellular factors for its optimal function

Navigating the integration of biotic interactions in biogeography

Biotic interactions are widely recognised as the backbone of ecological communities, but how best to study them is a subject of intense debate, especially at macro-ecological scales. While some researchers claim that biotic interactions need to be observed directly, others use proxies and statistical approaches to infer them. Despite this ambiguity, studying and predicting the influence of biotic interactions on biogeographic patterns is a thriving area of research with crucial implications for conservation. Three distinct approaches are currently being explored. The first approach involves empirical observation and measurement of biotic interactions' effects on species demography in laboratory or field settings. While these findings contribute to theory and to understanding species' demographies, they can be challenging to generalise on a larger scale. The second approach centers on inferring biotic associations from observed co-occurrences in space and time. The goal is to distinguish the environmental and biotic effects on species distributions. The third approach constructs extensive potential interaction networks, known as metanetworks, by leveraging existing knowledge about species ecology and interactions. This approach analyses local realisations of these networks using occurrence data and allows understanding large distributions of multi-taxa assemblages. In this piece, we appraise these three approaches, highlighting their respective strengths and limitations. Instead of seeing them as conflicting, we advocate for their integration to enhance our understanding and expand applications in the emerging field of interaction biogeography. This integration shows promise for ecosystem understanding and management in the Anthropocene era

In-situ characterization of the Hamamatsu R5912-HQE photomultiplier tubes used in the DEAP-3600 experiment

The Hamamatsu R5912-HQE photomultiplier-tube (PMT) is a novel high-quantum efficiency PMT. It is currently used in the DEAP-3600 dark matter detector and is of significant interest for future dark matter and neutrino experiments where high signal yields are needed. We report on the methods developed for in-situ characterization and monitoring of DEAP's 255 R5912-HQE PMTs. This includes a detailed discussion of typical measured single-photoelectron charge distributions, correlated noise (afterpulsing), dark noise, double, and late pulsing characteristics. The characterization is performed during the detector commissioning phase using laser light injected through a light diffusing sphere and during normal detector operation using LED light injected through optical fibres

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

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