Critical role of helix 12 of the vitamin D(3) receptor for the partial agonism of carboxylic ester antagonists.

The carboxy-terminal alpha-helix of a nuclear receptor ligand-binding domain (LBD), helix 12, contains a critical, ligand-modulated interface for the interaction with coactivator proteins. In this study, using the example of the vitamin D receptor (VDR) and the partial antagonist ZK159222, the role of helix 12 (residues 417-427) for both antagonistic and agonistic receptor actions was investigated. Amino acid residue G423 was demonstrated to be critical for partial agonism of ZK159222, but not for the activity of the natural VDR agonist, 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)). The amount of partial agonism of ZK159222 increased when helix 12 was truncated by the last four amino acid residues (Delta424-27) and augmented even more, when in addition helix 12 of VDR's dimerization partner, retinoid X receptor (RXR), was truncated. In contrast, the low agonism of a structural derivative of ZK159222, ZK168281, was not affected comparably, whereas other close structural relatives of ZK159222 even demonstrated the same agonistic activity as that of 1alpha,25(OH)(2)D(3). The amount of agonism of ZK159222 and ZK168281 at different variations of helix 12 correlated well with VDR's ability to complex with coactivator proteins and inversely correlated with the strength of the compound's antagonistic action on 1alpha,25(OH)(2)D(3) signalling. Molecular dynamics simulations of the LBD complexed with the two antagonists could explain their different action by demonstrating a more drastic displacement of helix 12 through ZK168281 than through ZK159222. Moreover, the modelling could indicate a kink of helix 12 at amino acid residue G423, which provides the last four amino acid residues of helix 12 with a modulatory role for the partial agonism of some VDR antagonists, such as ZK159222. In conclusion, partial agonism of a VDR antagonist is lower the more it disturbs helix 12 in taking the optimal position for coactivator interaction.     

Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding

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Island properties dominate species traits in determining plant colonizations in an archipelago system

The extrinsic determinants hypothesis emphasizes the essential role of environmental heterogeneity in species’ colonization. Consequently, high resident species diversity can increase community susceptibility to colonizations because good habitats may support more species that are functionally similar to colonizers. On the other hand, colonization success is also likely to depend on species traits. We tested the relative importance of environmental characteristics and species traits in determining colonization success using census data of 587 vascular plant species collected about 70 yr apart from 471 islands in the archipelago of SW Finland. More specifically, we explored potential new colonization as a function of island properties (e.g. location, area, habitat diversity, number of resident species per unit area), species traits (e.g. plant height, life-form, dispersal vector, Ellenberg indicator values, association with human impact), and species’ historical distributions (number of inhabited islands, nearest occurrence). Island properties and species’ historical distributions were more effective than plant traits in explaining colonization outcomes. Contrary to the extrinsic determinants hypothesis, colonization success was neither associated with resident species diversity nor habitat diversity per se, although colonization was lowest on sparsely vegetated islands. Our findings lead us to propose that while plant traits related to dispersal and establishment may enhance colonization, predictions of plant colonizations primarily require understanding of habitat properties and species’ historical distributions.     

NADPH-cytochrome-c-reductase: Changes in specific activity in gypsy moth larvae

NADPH-cytochrome-c-reductase from guts of gypsy moth, Porthetria dispar, oxidized NADPH at the following rates: 11·6, 41·9, and 57·6 nmol/30 min per 0·6 mg protein, in the third, fourth and fifth instar, respectively. The increase in specific activity may be due to a natural induction process controlled by materials in the food. This could also explain the observed decreases just prior to ecdysis at which time the larvae have ceased feeding.     

Perception of Graphical Virtual Environments by Blind Users via Sensory Substitution

Graphical virtual environments are currently far from accessible to blind users as their content is mostly visual. This is especially unfortunate as these environments hold great potential for this population for purposes such as safe orientation, education, and entertainment. Previous tools have increased accessibility but there is still a long way to go. Visual-to-audio Sensory-Substitution-Devices (SSDs) can increase accessibility generically by sonifying on-screen content regardless of the specific environment and offer increased accessibility without the use of expensive dedicated peripherals like electrode/vibrator arrays. Using SSDs virtually utilizes similar skills as when using them in the real world, enabling both training on the device and training on environments virtually before real-world visits. This could enable more complex, standardized and autonomous SSD training and new insights into multisensory interaction and the visually-deprived brain. However, whether congenitally blind users, who have never experienced virtual environments, will be able to use this information for successful perception and interaction within them is currently unclear.We tested this using the EyeMusic SSD, which conveys whole-scene visual information, to perform virtual tasks otherwise impossible without vision. Congenitally blind users had to navigate virtual environments and find doors, differentiate between them based on their features (Experiment1:task1) and surroundings (Experiment1:task2) and walk through them; these tasks were accomplished with a 95% and 97% success rate, respectively. We further explored the reactions of congenitally blind users during their first interaction with a more complex virtual environment than in the previous tasks–walking down a virtual street, recognizing different features of houses and trees, navigating to cross-walks, etc. Users reacted enthusiastically and reported feeling immersed within the environment. They highlighted the potential usefulness of such environments for understanding what visual scenes are supposed to look like and their potential for complex training and suggested many future environments they wished to experience.     

Attempts to determine the status of electroshock-induced attack in male laboratory mice

An attempt was made using a combination of simple experimental manipulations and videotape recorder (VTR) analysis of bite targets employed to determine whether electroshock-induced attack on anosmic opponents in laboratory mice was an offensive or a defensive behaviour. VTR analysis suggested that ventral surface biting was more evident in this form of attack than in social conflict. Individually- and group-housed males showed similar levels of fighting on exposure to electroshock, but dominant males from pairs showed greater attack than their subordinate partners. Zinc sulphate-induced anosmia, 36 h of food deprivation, castration and lithium chloride treatment reduced electroshock-induced attack. Although significant changes were not obtained, there was some evidence that acute treatment with dexamethasone or ACTH augmented this behaviour. The direction of these changes is similar to that seen with social conflict, and it is suggested that electroshock-induced attack in the mouse (unlike the rat) is largely an aggressive offensive behaviour. The high incidence of ventral surface biting may be a consequence of the upright postures assumed on subjecting the animals to electroshock.