Predictive coding of visual motion in both monocular and binocular human visual processing

Neural processing of sensory input in the brain takes time, and for that reason our awareness of visual events lags behind their actual occurrence. One way the brain might compensate to minimize the impact of the resulting delays is through extrapolation. Extrapolation mechanisms have been argued to underlie perceptual illusions in which moving and static stimuli are mislocalised relative to one another (such as the flash-lag and related effects). However, where in the visual hierarchy such extrapolation processes take place remains unknown. Here, we address this question by identifying monocular and binocular contributions to the flash-grab illusion. In this illusion, a brief target is flashed on a moving background that reverses direction. As a result, the perceived position of the target is shifted in the direction of the reversal. We show that the illusion is attenuated, but not eliminated, when the motion reversal and the target are presented dichoptically to separate eyes. This reveals extrapolation mechanisms at both monocular and binocular processing stages contribute to the illusion. We interpret the results in a hierarchical predictive coding framework, and argue that prediction errors in this framework manifest directly as perceptual illusions

Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 α-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein

[EN] Cell viability requires adaptation to changing environmental conditions. Ubiquitin-mediated endocytosis plays a crucial role in this process, because it provides a mechanism to remove transport proteins from the membrane. Arrestin-related trafficking proteins are important regulators of the endocytic pathway in yeast, facilitating selective ubiquitylation of target proteins by the E3 ubiquitin ligase, Rsp5. Specifically, Rod1 (Art4) has been reported to regulate the endocytosis of both the Hxt1, Hxt3, and Hxt6 glucose transporters and the Jen1 lactate transporter. Also, the AMP kinase homologue, Snf1, and 14-3-3 proteins have been shown to regulate Jen1 via Rod1. Here, we further characterized the role of Rod1, Snf1, and 14-3-3 in the signal transduction route involved in the endocytic regulation of the Hxt6 high affinity glucose transporter by showing that Snf1 interacts specifically with Rod1 and Rog3 (Art7), that the interaction between the Bmh2 and several arrestin-related trafficking proteins may be modulated by carbon source, and that both the 14-3-3 protein Bmh2 and the Snf1 regulatory domain interact with the arrestin-like domain containing the N-terminal half of Rod1 (amino acids 1-395). Finally, using both co-immunoprecipitation and bimolecular fluorescence complementation, we demonstrated the interaction of Rod1 with Hxt6 and showed that the localization of the Rod1-Hxt6 complex at the plasma membrane is affected by carbon source and is reduced upon overexpression of SNF1 and BMH2.Supported by a predoctoral fellowship from the Polytechnic University of Valencia.Llopis Torregrosa, V.; Ferri-Blazquez, A.; Adam-Artigues, A.; Deffontaines, E.; Van Heusden, GPH.; Yenush, L. (2016). Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 α-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein. Journal of Biological Chemistry. 291(29):14973-14985. https://doi.org/10.1074/jbc.M116.733923S149731498529129Mulet, J. M., Llopis-Torregrosa, V., Primo, C., Marqués, M. C., & Yenush, L. (2013). Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants. 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Journal of Biological Chemistry, 288(33), 24063-24080. doi:10.1074/jbc.m113.478511O’Donnell, A. F., McCartney, R. R., Chandrashekarappa, D. G., Zhang, B. B., Thorner, J., & Schmidt, M. C. (2014). 2-Deoxyglucose Impairs Saccharomyces cerevisiae Growth by Stimulating Snf1-Regulated and α-Arrestin-Mediated Trafficking of Hexose Transporters 1 and 3. Molecular and Cellular Biology, 35(6), 939-955. doi:10.1128/mcb.01183-14Becuwe, M., Vieira, N., Lara, D., Gomes-Rezende, J., Soares-Cunha, C., Casal, M., … Léon, S. (2012). A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis. The Journal of Cell Biology, 196(2), 247-259. doi:10.1083/jcb.201109113Alvaro, C. G., Aindow, A., & Thorner, J. (2016). Differential Phosphorylation Provides a Switch to Control How α-Arrestin Rod1 Down-regulates Mating Pheromone Response inSaccharomyces cerevisiae. Genetics, 203(1), 299-317. doi:10.1534/genetics.115.186122Alvaro, C. G., O’Donnell, A. F., Prosser, D. C., Augustine, A. A., Goldman, A., Brodsky, J. L., … Thorner, J. (2014). Specific  -Arrestins Negatively Regulate Saccharomyces cerevisiae Pheromone Response by Down-Modulating the G-Protein-Coupled Receptor Ste2. Molecular and Cellular Biology, 34(14), 2660-2681. doi:10.1128/mcb.00230-14Shinoda, J., & Kikuchi, Y. (2007). Rod1, an arrestin-related protein, is phosphorylated by Snf1-kinase in Saccharomyces cerevisiae. Biochemical and Biophysical Research Communications, 364(2), 258-263. doi:10.1016/j.bbrc.2007.09.134Ichimura, T., Yamamura, H., Sasamoto, K., Tominaga, Y., Taoka, M., Kakiuchi, K., … Isobe, T. (2005). 14-3-3 Proteins Modulate the Expression of Epithelial Na+Channels by Phosphorylation-dependent Interaction with Nedd4-2 Ubiquitin Ligase. Journal of Biological Chemistry, 280(13), 13187-13194. doi:10.1074/jbc.m412884200Bhalla, V., Daidié, D., Li, H., Pao, A. C., LaGrange, L. P., Wang, J., … Pearce, D. (2005). Serum- and Glucocorticoid-Regulated Kinase 1 Regulates Ubiquitin Ligase Neural Precursor Cell-Expressed, Developmentally Down-Regulated Protein 4-2 by Inducing Interaction with 14-3-3. Molecular Endocrinology, 19(12), 3073-3084. doi:10.1210/me.2005-0193Jiang, R., & Carlson, M. (1996). Glucose regulates protein interactions within the yeast SNF1 protein kinase complex. Genes & Development, 10(24), 3105-3115. doi:10.1101/gad.10.24.3105Proszynski, T. J., Klemm, R. W., Gravert, M., Hsu, P. P., Gloor, Y., Wagner, J., … Walch-Solimena, C. (2005). A genome-wide visual screen reveals a role for sphingolipids and ergosterol in cell surface delivery in yeast. Proceedings of the National Academy of Sciences, 102(50), 17981-17986. doi:10.1073/pnas.0509107102MacGurn, J. A., Hsu, P.-C., & Emr, S. D. (2012). Ubiquitin and Membrane Protein Turnover: From Cradle to Grave. Annual Review of Biochemistry, 81(1), 231-259. doi:10.1146/annurev-biochem-060210-093619Becuwe, M. , and Léon, S. 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Inhibition of all-TRANS-retinoic acid metabolism by R116010 induces antitumour activity

All-trans-retinoic acid is a potent inhibitor of cell proliferation and inducer of differentiation. However, the clinical use of all-trans-retinoic acid in the treatment of cancer is significantly hampered by its toxicity and the prompt emergence of resistance, believed to be caused by increased all-trans-retinoic acid metabolism. Inhibitors of all-trans-retinoic acid metabolism may therefore prove valuable in the treatment of cancer. In this study, we characterize R116010 as a new anticancer drug that is a potent inhibitor of all-trans-retinoic acid metabolism. In vitro, R116010 potently inhibits all-trans-retinoic acid metabolism in intact T47D cells with an IC50-value of 8.7 nM. In addition, R116010 is a selective inhibitor as indicated by its inhibition profile for several other cytochrome P450-mediated reactions. In T47D cell proliferation assays, R116010 by itself has no effect on cell proliferation. However, in combination with all-trans-retinoic acid, R116010 enhances the all-trans-retinoic acid-mediated antiproliferative activity in a concentration-dependent manner. In vivo, the growth of murine oestrogen-independent TA3-Ha mammary tumours is significantly inhibited by R116010 at doses as low as 0.16 mg kg−1. In conclusion, R116010 is a highly potent and selective inhibitor of all-trans-retinoic acid metabolism, which is able to enhance the biological activity of all-trans-retinoic acid, thereby exhibiting antitumour activity. R116010 represents a novel and promising anticancer drug with an unique mechanism of action

Raamwerk voor omgaan met onzekerheid

In de nieuwe Wro staat dat nieuwe ruimtelijke plannen vanaf 1 januari 2010 digitaal en uitwisselbaar vervaardigd moeten worden. Het digitaliseren van het ruimtelijke ordeningsproces heeft een grote impact. Het zou het vergelijken van plannen eenvoudiger moeten maken, maar vooral onzekere planobjecten kunnen lastig zijn bij het vergelijken van plannen. De taxonomie voor onzekerheid in de ruimtelijke ordening is de basis voor het raamwerk. In het raamwerk worden alle bronnen van onzekerheid die in de ruimtelijke ordening aanwezig zijn besproken en er worden omgangsvormen aangeboden

Graphical analysis and experimental evaluation of Saccharomyces cerevisiae P_TRK1|2 and P_BMH1|2 promoter region

Plant sciencesMicrobial Biotechnolog

Tomato breeding in the genomics era: insights from a SNP array

Background - The major bottle neck in genetic and linkage studies in tomato has been the lack of a sufficient number of molecular markers. This has radically changed with the application of next generation sequencing and high throughput genotyping. A set of 6000 SNPs was identified and 5528 of them were used to evaluate tomato germplasm at the level of species, varieties and segregating populations. Results - From the 5528 SNPs, 1980 originated from 454-sequencing, 3495 from Illumina Solexa sequencing and 53 were additional known markers. Genotyping different tomato samples allowed the evaluation of the level of heterozygosity and introgressions among commercial varieties. Cherry tomatoes were especially different from round/beefs in chromosomes 4, 5 and 12. We were able to identify a set of 750 unique markers distinguishing S. lycopersicum 'Moneymaker' from all its distantly related wild relatives. Clustering and neighbour joining analysis among varieties and species showed expected grouping patterns, with S. pimpinellifolium as the most closely related to commercial tomatoesearlier results. Conclusions - Our results show that a SNP search in only a few breeding lines already provides generally applicable markers in tomato and its wild relatives. It also shows that the Illumina bead array generated data are highly reproducible. Our SNPs can roughly be divided in two categories: SNPs of which both forms are present in the wild relatives and in domesticated tomatoes (originating from common ancestors) and SNPs unique for the domesticated tomato (originating from after the domestication event). The SNPs can be used for genotyping, identification of varieties, comparison of genetic and physical linkage maps and to confirm (phylogenetic) relations. In the SNPs used for the array there is hardly any overlap with the SolCAP array and it is strongly recommended to combine both SNP sets and to select a core collection of robust SNPs completely covering the entire tomato genom

The long and winding road leading to the successful introgression of downy mildew resistance into onion

Downy mildew resistance originating from Allium roylei Stearn provides a complete resistance to onions and is based on one, dominant gene. Since A. roylei can successfully be hybridized with onion (A. cepa L.), a breeding scheme aimed at the introgression of this gene was initiated ca. 20 years ago. Several setbacks in this programme were encountered, firstly the identified molecular marker linked to the downy mildew resistance locus became increasingly difficult to use and finally lost its discriminating power and secondly the final step, making homozygous introgression lines (ILs), turned out to be more difficult then was hoped. GISH analysis showed that the chromosomal region harbouring the resistance locus was the only remaining piece of A. roylei in the nuclear background of onion and it also confirmed that this region was located on the distal end of chromosome 3. It was hypothesized that some factor present in the remaining A. roylei region was lethal when homozygously present in an onion genetic background. The identification of an individual with a smaller and more distally located introgression fragment and homozygous ILs in its progeny validated this hypothesis. With the help of these nearly isogenic lines four AFLP® markers closely linked to the resistance gene were identified, which can be used for marker-aided selection. The introduction of downy mildew resistance caused by Peronospora destructor into onion is a significant step forward in the development of environmentally-friendly onion cultivars.<br/>Downy mildew resistance originating from Allium roylei Stearn provides a complete resistance to onions and is based on one, dominant gene. Since A. roylei can successfully be hybridized with onion (A. cepa L.), a breeding scheme aimed at the introgression of this gene was initiated ca. 20 years ago. Several setbacks in this programme were encountered, firstly the identified molecular marker linked to the downy mildew resistance locus became increasingly difficult to use and finally lost its discriminating power and secondly the final step, making homozygous introgression lines (ILs), turned out to be more difficult then was hoped. GISH analysis showed that the chromosomal region harbouring the resistance locus was the only remaining piece of A. roylei in the nuclear background of onion and it also confirmed that this region was located on the distal end of chromosome 3. It was hypothesized that some factor present in the remaining A. roylei region was lethal when homozygously present in an onion genetic background. The identification of an individual with a smaller and more distally located introgression fragment and homozygous ILs in its progeny validated this hypothesis. With the help of these nearly isogenic lines four AFLP (R) markers closely linked to the resistance gene were identified, which can be used for marker-aided selection. The introduction of downy mildew resistance caused by Peronospora destructor into onion is a significant step forward in the development of environmentally-friendly onion cultivars

Unrelated Helpers in a Primitively Eusocial Wasp: Is Helping Tailored Towards Direct Fitness?

The paper wasp Polistes dominulus is unique among the social insects in that nearly one-third of co-foundresses are completely unrelated to the dominant individual whose offspring they help to rear and yet reproductive skew is high. These unrelated subordinates stand to gain direct fitness through nest inheritance, raising the question of whether their behaviour is adaptively tailored towards maximizing inheritance prospects. Unusually, in this species, a wealth of theory and empirical data allows us to predict how unrelated subordinates should behave. Based on these predictions, here we compare helping in subordinates that are unrelated or related to the dominant wasp across an extensive range of field-based behavioural contexts. We find no differences in foraging effort, defense behaviour, aggression or inheritance rank between unrelated helpers and their related counterparts. Our study provides no evidence, across a number of behavioural scenarios, that the behaviour of unrelated subordinates is adaptively modified to promote direct fitness interests