Inverse agonist efficacy of selatogrel blunts constitutive P2Y12 receptor signaling by inducing the inactive receptor conformation.

Selatogrel is a potent inhibitor of adenosine diphosphate (ADP) binding to the P2Y12 receptor, preventing platelet activation. We have previously shown that the P2Y12 receptor constitutively activates Gi- and Go-protein-mediated signaling in human platelets. Here, we report that selatogrel acts as an inverse agonist of the P2Y12 receptor.

Multifunctional Contribution of the Inflated Fruiting Calyx: Implication for Cuticular Barrier Profiles of the Solanaceous Genera , and .

Pivotal barrier properties of the hydrophobic plant cuticle covering aerial plant surfaces depend on its physicochemical composition. Among plant species and organs, compounds of this boundary layer between the plant interior and the environment vary considerably but cuticle-related studies comparing different organs from the same plant species are still scarce. Thus, this study focused on the cuticle profiles of , and species.

Building a Barrier: The Influence of Different Wax Fractions on the Water Transpiration Barrier of Leaf Cuticles.

Waxes are critical in limiting non-stomatal water loss in higher terrestrial plants by making up the limiting barrier for water diffusion across cuticles. Using a differential extraction protocol, we investigated the influence of various wax fractions on the cuticular transpiration barrier. Triterpenoids (TRPs) and very long-chain aliphatics (VLCAs) were selectively extracted from isolated adaxial leaf cuticles using methanol (MeOH) followed by chloroform (TCM).

The P2Y12 Receptor Antagonist Selatogrel Dissolves Preformed Platelet Thrombi In Vivo.

Selatogrel, a potent and reversible antagonist of the P2Y12 receptor, inhibited FeCl-induced thrombosis in rats. Here, we report the anti-thrombotic effect of selatogrel after subcutaneous applications in guinea pigs and mice. Selatogrel inhibited platelet function only 10 min after subcutaneous application in mice.

Large differences in leaf cuticle conductance and its temperature response among 24 tropical tree species from across a rainfall gradient.

More frequent droughts and rising temperatures pose serious threats to tropical forests. When stomata are closed under dry and hot conditions, plants lose water through leaf cuticles, but little is known about cuticle conductance (g ) of tropical trees, how it varies among species and environments, and how it is affected by temperature. We determined g in relation to temperature for 24 tropical tree species across a steep rainfall gradient in Panama, by recording leaf drying curves at different temperatures in the laboratory.

Selatogrel, a reversible P2Y12 receptor antagonist, has reduced off-target interference with haemostatic factors in a mouse thrombosis model.

Introduction: Selatogrel is a reversible antagonist of the P2Y12 receptor. In rat thrombosis/haemostasis models, selatogrel was associated with lower blood loss than clopidogrel or ticagrelor at equivalent anti-thrombotic effect.

Material And Methods: We sought to elucidate the mechanism underlying the observed differences in blood loss, using real-time intravital microscopy in mouse.

Optogenetic control of plant growth by a microbial rhodopsin.

While rhodopsin-based optogenetics has revolutionized neuroscience, poor expression of opsins and the absence of the essential cofactor all-trans-retinal has complicated the application of rhodopsins in plants. Here, we demonstrate retinal production in plants and improved rhodopsin targeting for green light manipulation of plant cells using the Guillardia theta light-gated anion channelrhodopsin GtACR1. Green light induces a massive increase in anion permeability and pronounced membrane potential changes when GtACR1 is expressed, enabling non-invasive manipulation of plant growth and leaf development.

The potency of selatogrel, a reversible antagonist of the P2Y12 receptor, is affected by calcium concentration.

Here, we report the characterization of the P2Y12 receptor antagonist selatogrel (ACT-246475). Binding studies with radiolabeled selatogrel demonstrated that selatogrel is a competitive antagonist of ADP binding to the P2Y12 receptor with a fast onset of action. Consequently, selatogrel was confirmed to be a potent inhibitor of P2Y12-mediated intra-platelet signaling and ADP-induced platelet activation.

Insights from In Vitro and Clinical Data to Guide Transition from the Novel P2Y12 Antagonist Selatogrel to Clopidogrel, Prasugrel, and Ticagrelor.

Reduced pharmacodynamic (PD) effects of irreversible oral P2Y receptor antagonists have been reported when administered during cangrelor infusion. Therefore, the PD interaction liability of the novel P2Y receptor antagonist selatogrel with irreversible (i.e.

Compositional, structural and functional cuticle analysis of Prunus laurocerasus L. sheds light on cuticular barrier plasticity.

Barrier properties of the hydrophobic plant cuticle depend on its physicochemical composition. The cuticular compounds vary considerably among plant species but also among organs and tissues of the same plant and throughout developmental stages. As yet, these intraspecific modifications at the cuticular wax and cutin level are only rarely examined.

Leaf cuticle analyses: implications for the existence of cutan/non-ester cutin and its biosynthetic origin.

Background And Aims: The cuticle of a limited number of plant species contains cutan, a chemically highly resistant biopolymer. As yet, the biosynthesis of cutan is not fully understood. Attempting to further unravel the origin of cutan, we analysed the chemical composition of enzymatically isolated cuticular membranes of Agave americana leaves.

Insights Into Olive Fruit Surface Functions: A Comparison of Cuticular Composition, Water Permeability, and Surface Topography in Nine Cultivars During Maturation.

Olive ( L.) growing has outstanding economic relevance in Spain, the main olive oil producer and exporter in the world. Fruit skin properties are very relevant for fruit and oil quality, water loss, and susceptibility to mechanical damage, rots, and infestations, but limited research focus has been placed on the cuticle of intact olive fruit.

Cuticular wax coverage and its transpiration barrier properties in Quercus coccifera L. leaves: does the environment matter?

Plants prevent uncontrolled water loss by synthesizing, depositing and maintaining a hydrophobic layer over their primary aerial organs-the plant cuticle. Quercus coccifera L. can plastically respond to environmental conditions at the cuticular level.

Cuticular wax coverage and its transpiration barrier properties in Quercus coccifera L. leaves: does the environment matter?

Plants prevent uncontrolled water loss by synthesizing, depositing and maintaining a hydrophobic layer over their primary aerial organs-the plant cuticle. Quercus coccifera L. can plastically respond to environmental conditions at the cuticular level.

The permeation barrier of plant cuticles: uptake of active ingredients is limited by very long-chain aliphatic rather than cyclic wax compounds.

Background: The barrier to diffusion of organic solutes across the plant cuticle is composed of waxes consisting of very long-chain aliphatic (VLCA) and, to varying degrees, cyclic compounds like pentacyclic triterpenoids. The roles of both fractions in controlling cuticular penetration by organic solutes, e.g.

UV-C irradiation compromises conidial germination, formation of appressoria, and induces transcription of three putative photolyase genes in the barley powdery mildew fungus, Blumeria graminis f. sp. hordei.

UV-C irradiation is known to compromise germination of Blumeria graminis conidia and to reduce powdery mildew infestation. However, only scarce information is available on the effects of UV-C irradiation on B. graminis appressorium formation.

Effects of temperature on the cuticular transpiration barrier of two desert plants with water-spender and water-saver strategies.

The efficacy of the cuticular transpiration barrier and its resistance to elevated temperatures are significantly higher in a typical water-saver than in a water-spender plant growing in hot desert.

The Mode of Action of Adjuvants-Relevance of Physicochemical Properties for Effects on the Foliar Application, Cuticular Permeability, and Greenhouse Performance of Pinoxaden.

We comprehensively studied the complexity of the mode of action of adjuvants by uncoupling the parameters contributing to the spray process during foliar application of agrochemicals. The ethoxylated sorbitan esters Tween 20 and Tween 80 improved the efficiency of pinoxaden (PXD) in controlling grass-weed species in greenhouse experiments by aiding retention, having humectant properties, maintaining the bioavailability, and increasing the cuticular penetration of PXD. The nonethoxylated sorbitan esters Span 20 and Span 80 showed minimal effects on retention, droplet hydration, or cuticular penetration, resulting in reduced PXD effects in the greenhouse.

Direct Effects of Physcion, Chrysophanol, Emodin, and Pachybasin on Germination and Appressorium Formation of the Barley ( Hordeum vulgare L.) Powdery Mildew Fungus Blumeria graminis f. sp. hordei (DC.) Speer.

Several anthraquinone derivatives are active components of fungicidal formulations particularly effective against powdery mildew fungi. The antimildew effect of compounds such as physcion and chrysophanol is largely attributed to host plant defense induction. However, so far a direct fungistatic/fungicidal effect of anthraquinone derivatives on powdery mildew fungi has not been unequivocally demonstrated.

The ecophysiology of leaf cuticular transpiration: are cuticular water permeabilities adapted to ecological conditions?

When the stomata are closed under drought, the only route for water loss from the leaf interior to the atmosphere is across the cuticle. Thus, the extent of cuticular transpiration in relation to the reservoirs of water in the plant and the water acquisition from the soil determines the fitness and survival of the plant. It is, therefore, widely assumed that the cuticular water permeability of plants regularly experiencing drought is comparatively low and, thus, adapted to the environment.

Chemical Composition and Water Permeability of Fruit and Leaf Cuticles of Olea europaea L.

The plant cuticle, protecting against uncontrolled water loss, covers olive (Olea europaea) fruits and leaves. The present study describes the organ-specific chemical composition of the cuticular waxes and the cutin and compares three developmental stages of fruits (green, turning, and black) with the leaf surface. Numerous organ-specific differences, such as the total coverage of cutin monomeric components (1034.

The reversible P2Y antagonist ACT-246475 causes significantly less blood loss than ticagrelor at equivalent antithrombotic efficacy in rat.

The P2Y receptor is a validated target for prevention of major adverse cardiovascular events in patients with acute coronary syndrome. The aim of this study was to compare two direct-acting, reversible P2Y antagonists, ACT-246475 and ticagrelor, in a rat thrombosis model by simultaneous quantification of their antithrombotic efficacy and surgery-induced blood loss. Blood flow velocity was assessed in the carotid artery after FeCl -induced thrombus formation using a Doppler flow probe.

Very-long-chain aldehydes induce appressorium formation in ascospores of the wheat powdery mildew fungus Blumeria graminis.

Asexually produced conidia of the wheat powdery mildew fungus Blumeria graminis f. sp. tritici (Bgt) are known to perceive cuticular very-long-chain aldehydes as signal substances strongly stimulating germination and differentiation of infection structures in a concentration- and chain-length-dependent manner.