Search

Although humans have long been predators with enduring nutritive and cultural relationships with their prey, seldom have conservation ecologists considered the divergent predatory behavior of contemporary, industrialized humans. Recognizing that the number, strength and diversity of predator-prey relationships can profoundly influence biodiversity, here we analyze humanity's modern day predatory interactions with vertebrates and estimate their ecological consequences. Analysing IUCN 'use and trade' data for ~47,000 species, we show that fishers, hunters and other animal collectors prey on more than a third (~15,000 species) of Earth's vertebrates. Assessed over equivalent ranges, humans exploit up to 300 times more species than comparable non-human predators. Exploitation for the pet trade, medicine, and other uses now affects almost as many species as those targeted for food consumption, and almost 40% of exploited species are threatened by human use. Trait space analyses show that birds and mammals threatened by exploitation occupy a disproportionally large and unique region of ecological trait space, now at risk of loss. These patterns suggest far more species are subject to human-imposed ecological (e.g., landscapes of fear) and evolutionary (e.g., harvest selection) processes than previously considered. Moreover, continued overexploitation will likely bear profound consequences for biodiversity and ecosystem function. Predatory niche and ecological trait space analyses identify modern humans as unique predators of vertebrates. [ABSTRACT FROM AUTHOR]

Protease-activated receptor-2 (PAR2) has been implicated in multiple pathophysiologies but drug discovery is challenging due to low small molecule tractability and a complex activation mechanism. Here we report the pharmacological profiling of a potent new agonist, suggested by molecular modelling to bind in the putative orthosteric site, and two novel PAR2 antagonists with distinctly different mechanisms of inhibition. We identify coupling between different PAR2 binding sites. One antagonist is a competitive inhibitor that binds to the orthosteric site, while a second antagonist is a negative allosteric modulator that binds at a remote site. The allosteric modulator shows probe dependence, more effectively inhibiting peptide than protease activation of PAR2 signalling. Importantly, both antagonists are active in vivo, inhibiting PAR2 agonist-induced acute paw inflammation in rats and preventing activation of mast cells and neutrophils. These results highlight two distinct mechanisms of inhibition that potentially could be targeted for future development of drugs that modulate PAR2. Kennedy et al. report the pharmacological and in vivo profiling of two small molecule PAR2 inhibitors and an agonist. They conclude that while the small molecule agonist and one of the inhibitors bind to the orthosteric PAR2 binding site, the other inhibitor is a negative allosteric modulator, highlighting two distinct mechanisms of inhibition that could be targeted for future development of drugs that modulate PAR2. [ABSTRACT FROM AUTHOR]

In an attempt to better constrain the timing of Variscan HP-HT metamorphism in the SE Bohemian Massif we have dated zoned zircons from a garnet-kyanite granulite of granitic composition from the Dunkelsteiner Wald Massif, Lower Austria, by means of sensitive high-resolution ion microprobe (SHRIMP) technique. In order to combine isotopic information with crystal growth textures, CL and BSE images were systematically taken from the dated zircons. A characteristic threefold concentric zoning was found in many zircons. This involves pre-Variscan protolithic cores followed by two distinct metamorphic/anatectic overgrowth shells of Variscan age. The inner overgrowth shell is characterized by a weak CL but bright BSE signal, and yields high contents of uranium (0.1 to 0.2 wt.%). A pooled U-Pb Concordia age for this zone is 342.0 ± 3.0 Ma ( n = 11, MSWD = 0.12). The second, outer, overgrowth shell is always bright in the CL image, dark in the BSE image, and has generally low uranium contents (mostly <500 ppm). A pooled U-Pb Concordia age for this zone is 337.1 ± 2.7 Ma ( n = 11, MSWD = 0.22). These results imply that the Variscan HT crystallisation history of the Moldanubian granulites took place over a period of a few million years and was not an extremely rapid subduction-exhumation process. SHRIMP measurements in the protolithic cores yield a cluster of (sub)concordant ages between ∼390 and 460 Ma and a few outliers at higher ages mostly represented by cores in cores. Core domains, which are large, homogeneous and with undisturbed igneous oscillatory zoning, yielded preferentially ages between 430 and 460 Ma. We therefore consider that granitic protolith formation took place at that time. The still older inner cores are interpreted as inherited into the granitic melt. [ABSTRACT FROM AUTHOR]