Functional selectivity of adenosine receptor ligands

Adenosine receptors are plasma membrane proteins that transduce an extracellular signal into the interior of the cell. Basically every mammalian cell expresses at least one of the four adenosine receptor subtypes. Recent insight in signal transduction cascades teaches us that the current classification of receptor ligands into agonists, antagonists, and inverse agonists relies very much on the experimental setup that was used. Upon activation of the receptors by the ubiquitous endogenous ligand adenosine they engage classical G protein-mediated pathways, resulting in production of second messengers and activation of kinases. Besides this well-described G protein-mediated signaling pathway, adenosine receptors activate scaffold proteins such as β-arrestins. Using innovative and sensitive experimental tools, it has been possible to detect ligands that preferentially stimulate the β-arrestin pathway over the G protein-mediated signal transduction route, or vice versa. This phenomenon is referred to as functional selectivity or biased signaling and implies that an antagonist for one pathway may be a full agonist for the other signaling route. Functional selectivity makes it necessary to redefine the functional properties of currently used adenosine receptor ligands and opens possibilities for new and more selective ligands. This review focuses on the current knowledge of functionally selective adenosine receptor ligands and on G protein-independent signaling of adenosine receptors through scaffold proteins

Antipredator behaviours of a spider mite in response to cues of dangerous and harmless predators

Prey are known to invest in costly antipredator behaviour when perceiving cues of dangerous, but not of relatively harmless predators. Whereas most studies investigate one type of antipredator behaviour, we studied several types (changes in oviposition, in escape and avoidance behaviour) in the spider mite Tetranychus evansi in response to cues from two predatory mites. The predator Phytoseiulus longipes is considered a dangerous predator for T. evansi, whereas Phytoseiulus macropilis has a low predation rate on this prey, thus is a much less dangerous predator. Spider mite females oviposited less on leaf disc halves with predator cues than on clean disc halves, independent of the predator species. On entire leaf discs, they laid fewer eggs in the presence of cues of the dangerous predator than on clean discs, but not in the presence of cues of the harmless predator. Furthermore, the spider mites escaped more often from discs with cues of the dangerous predator than from discs without predator cues, but they did not escape more from discs with cues of the harmless predator. The spider mites did not avoid plants with conspecifics and predators. We conclude that the spider mites displayed several different antipredator responses to the same predator species, and that some of these antipredator responses were stronger with cues of dangerous predators than with cues of harmless predators

Development of Plasma Vitellogenin Assay for Estrogenic Effects of Endocrine-Disrupting Chemicals Using Ovariectomized Goldfish (Carassius auratus)

Plasma vitellogenin (VTG) assay was developed using ovariectomized goldfish (Carassius auratus) for determining the estrogenic effects of endocrine-disrupting chemicals. In a laboratory study, we assessed the estrogenic activity of commercial fish diets by using a diet for ornamental carp (CD) and a casein-based formulated fish diet (FD), which was shown to not contain soybean or fish meal in a previous study. In ovariectomized fish, plasma VTG concentrations were significantly higher in the CD-fed group than in the FD-fed group. These results indicate that the estrogen activity of CD may be high enough to cause induction of plasma VTG in ovariectomized goldfish as previously observed in male goldfish. Moreover, the effect of estrogen on plasma VTG induction was confirmed by significant plasma VTG production following the exposure of FD-fed ovariectomized goldfish to a nominal estradiol-17β concentration of 100 μg/l for 31 days. Our data suggest that induction of plasma VTG using ovariectomized goldfish is a good tool for evaluating the estrogenic effects of endocrine-disrupting chemicals

Learners’ and teachers’ beliefs about learning tones and pinyin

This paper reports a study of the perceptions of English-speaking learners and teachers about the challenges and difficulties of Chinese as a Second Language (CSL) learning in England. The study involved a Likert-scale questionnaire and follow-up interviews with 37 university student learners, 443 school students and the 42 teachers of both groups. The questionnaires and interviews explored beliefs about language learning, about Chinese language learning and about language learning strategies. This paper focuses on the findings concerning the perceived challenges of speaking Chinese and of tones in learning Chinese. The findings of this study present a picture of teachers who are keen for their students to learn to speak and communicate in Chinese, and of students who are keen to take risks in speaking. However, in contrast to earlier findings about learners’ views about learning Chinese, the learners in this study claimed to be very tone aware and reported that they found listening and understanding Chinese more difficult than production. This is explored in relation to the pupils’ views about learning tones and pinyin and raises questions about the ways they address tones and pinyin learning in the context of their expressed aim of communicating and taking risks in speaking. The discussion raises issues about the possible effects of communicative teaching of languages in English schools. We ask whether an emphasis on communicative approaches may affect how learners address difficulties of the Chinese pronunciation system and the use of pinyin

What do contrast threshold equivalent noise studies actually measure? Noise vs. nonlinearity in different masking paradigms

The internal noise present in a linear system can be quantified by the equivalent noise method. By measuring the effect that applying external noise to the system’s input has on its output one can estimate the variance of this internal noise. By applying this simple “linear amplifier” model to the human visual system, one can entirely explain an observer’s detection performance by a combination of the internal noise variance and their efficiency relative to an ideal observer. Studies using this method rely on two crucial factors: firstly that the external noise in their stimuli behaves like the visual system’s internal noise in the dimension of interest, and secondly that the assumptions underlying their model are correct (e.g. linearity). Here we explore the effects of these two factors while applying the equivalent noise method to investigate the contrast sensitivity function (CSF). We compare the results at 0.5 and 6 c/deg from the equivalent noise method against those we would expect based on pedestal masking data collected from the same observers. We find that the loss of sensitivity with increasing spatial frequency results from changes in the saturation constant of the gain control nonlinearity, and that this only masquerades as a change in internal noise under the equivalent noise method. Part of the effect we find can be attributed to the optical transfer function of the eye. The remainder can be explained by either changes in effective input gain, divisive suppression, or a combination of the two. Given these effects the efficiency of our observers approaches the ideal level. We show the importance of considering these factors in equivalent noise studies