Id Gene regulation and function in the prosensory domains of the chicken inner ear: a link between Bmp Signaling and Atoh1

Bone morphogenetic proteins (Bmps) regulate the expression of the proneural gene Atoh1 and the generation of hair cells in the developing inner ear. The present work explored the role of Inhibitor of Differentiation genes (Id1-3) in this process. The results show that Id genes are expressed in the prosensory domains of the otic vesicle, along with Bmp4 and Bmp7. Those domains exhibit high levels of the phosphorylated form of Bmp-responding R-Smads (P-Smad1,5,8), and of Bmp-dependent Smad transcriptional activity as shown by the BRE-tk-EGFP reporter. Increased Bmp signaling induces the expression of Id1-3 along with the inhibition of Atoh1. Conversely, the Bmp antagonist Noggin or the Bmp-receptor inhibitor Dorsomorphin elicit opposite effects, indicating that Bmp signaling is necessary for Id expression and Atoh1 regulation in the otocyst. The forced expression of Id3 is sufficient to reduce Atoh1 expression and to prevent the expression of hair cell differentiation markers. Together, these results suggest that Ids are part of the machinery that mediates the regulation of hair cell differentiation exerted by Bmps. In agreement with that, during hair cell differentiation Bmp4 expression, P-Smad1,5,8 levels and Id expression are downregulated from hair cells. However, Ids are also downregulated from the supporting cells which contrarily to hair cells exhibit high levels of Bmp4 expression, P-Smad1,5,8, and BRE-tk-EGFP activity, suggesting that in these cells Ids escape from Bmp/Smad signaling. The differential regulation of Ids in time and space may underlie the multiple functions of Bmp signaling during sensory organ development.

How we experience immersive virtual environments: the concept of presence and its measurement

This paper reviews the concept of presence in immersive virtual environments, the sense of being there signalled by people acting and responding realistically to virtual situations and events. We argue that presence is a unique phenomenon that must be distinguished from the degree of engagement, involvement in the portrayed environment. We argue that there are three necessary conditions for presence: the (a) consistent low latency sensorimotor loop between sensory data and proprioception; (b) statistical plausibility: images must be statistically plausible in relation to the probability distribution of images over natural scenes. A constraint on this plausibility is the level of immersion;(c) behaviour-response correlations: Presence may be enhanced and maintained over time by appropriate correlations between the state and behaviour of participants and responses within the environment, correlations that show appropriate responses to the activity of the participants. We conclude with a discussion of methods for assessing whether presence occurs, and in particular recommend the approach of comparison with ground truth and give some examples of this.

Efficacy of a dilemma-focused intervention for unipolar depression: study protocol for a multicenter randomized controlled trial

Background Depression is one of the more severe and serious health problems because of its morbidity, disabling effects and for its societal and economic burden. Despite the variety of existing pharmacological and psychological treatments, most of the cases evolve with only partial remission, relapse and recurrence. Cognitive models have contributed significantly to the understanding of unipolar depression and its psychological treatment. However, success is only partial and many authors affirm the need to improve those models and also the treatment programs derived from them. One of the issues that requires further elaboration is the difficulty these patients experience in responding to treatment and in maintaining therapeutic gains across time without relapse or recurrence. Our research group has been working on the notion of cognitive conflict viewed as personal dilemmas according to personal construct theory. We use a novel method for identifying those conflicts using the repertory grid technique (RGT). Preliminary results with depressive patients show that about 90% of them have one or more of those conflicts. This fact might explain the blockage and the difficult progress of these patients, especially the more severe and/or chronic. These results justify the need for specific interventions focused on the resolution of these internal conflicts. This study aims to empirically test the hypothesis that an intervention focused on the dilemma(s) specifically detected for each patient will enhance the efficacy of cognitive behavioral therapy (CBT) for depression. Design A therapy manual for a dilemma-focused intervention will be tested using a randomized clinical trial by comparing the outcome of two treatment conditions: combined group CBT (eight, 2-hour weekly sessions) plus individual dilemma-focused therapy (eight, 1-hour weekly sessions) and CBT alone (eight, 2-hour group weekly sessions plus eight, 1-hour individual weekly sessions). Method Participants are patients aged over 18 years meeting diagnostic criteria for major depressive disorder or dysthymic disorder, with a score of 19 or above on the Beck depression inventory, second edition (BDI-II) and presenting at least one cognitive conflict (implicative dilemma or dilemmatic construct) as assessed using the RGT. The BDI-II is the primary outcome measure, collected at baseline, at the end of therapy, and at 3- and 12-month follow-up; other secondary measures are also used. Discussion We expect that adding a dilemma-focused intervention to CBT will increase the efficacy of one of the more prestigious therapies for depression, thus resulting in a significant contribution to the psychological treatment of depression. Trial registration ISRCTN92443999; ClinicalTrials.gov Identifier: NCT01542957.

An Analysis of Eye Scanpath Entropy in a Progressively Forming Virtual Environment

A sign of presence in virtual environments is that people respond to situations and events as if they were real, where response may be considered at many different levels, ranging from unconscious physiological responses through to overt behavior,emotions, and thoughts. In this paper we consider two responses that gave different indications of the onset of presence in a gradually forming environment. Two aspects of the response of people to an immersive virtual environment were recorded: their eye scanpath, and their skin conductance response (SCR). The scenario was formed over a period of 2 min, by introducing an increasing number of its polygons in random order in a head-tracked head-mounted display. For one group of experimental participants (n 8) the environment formed into one in which they found themselves standing on top of a 3 m high column. For a second group of participants (n 6) the environment was otherwise the same except that the column was only 1 cm high, so that they would be standing at normal ground level. For a third group of participants (n 14) the polygons never formed into a meaningful environment. The participants who stood on top of the tall column exhibited a significant decrease in entropy of the eye scanpath and an increase in the number of SCR by 99 s into the scenario, at a time when only 65% of the polygons had been displayed. The ground level participants exhibited a similar decrease in scanpath entropy, but not the increase in SCR. The random scenario grouping did not exhibit this decrease in eye scanpath entropy. A drop in scanpath entropy indicates that the environment had cohered into a meaningful perception. An increase in the rate of SCR indicates the perception of an aversive stimulus. These results suggest that on these two dimensions (scanpath entropy and rate of SCR) participants were responding realistically to the scenario shown in the virtual environment. In addition, the response occurred well before the entire scenario had been displayed, suggesting that once a set of minimal cues exists within a scenario,it is enough to form a meaningful perception. Moreover, at the level of the sympathetic nervous system, the participants who were standing on top of the column exhibited arousal as if their experience might be real. This is an important practical aspect of the concept of presence.

Potential of local bio-geoengineering to mitigate dangerous temperature increases in a global warming scenario

Crops and forests are already responding to rising atmospheric carbon dioxide and air temperatures. Increasing atmospheric CO2 concentrations are expected to enhance plant photosynthesis. Nevertheless, after long-term exposure, plants acclimate and show a reduction in photosynthetic activity (i.e. down-regulation). If in the future the Earth"s temperature is allowed to rise further, plant ecosystems and food security will both face significant threats. The scientific community has recognized that an increase in global temperatures should remain below 2°C in order to combat climate change. All this evidence suggests that, in parallel with reductions in CO2 emissions, a more direct approach to mitigate global warming should be considered. We propose here that global warming could be partially mitigated directly through local bio-geoengineering approaches. For example, this could be done through the management of solar radiation at surface level, i.e. by increasing global albedo. Such an effect has been documented in the south-eastern part of Spain, where a significant surface air temperature trend of -0.3°C per decade has been observed due to a dramatic expansion of greenhouse horticulture.

Characterization of an antennal carboxylesterase from the pest moth Spodoptera littoralis degrading a host plant odorant.

Background: Carboxyl/cholinesterases (CCEs) are highly diversified in insects. These enzymes have a broad range of proposed functions, in neuro/developmental processes, dietary detoxification, insecticide resistance or hormone/pheromone degradation. As few functional data are available on purified or recombinant CCEs, the physiological role of most of these enzymes is unknown. Concerning their role in olfaction, only two CCEs able to metabolize sex pheromones have been functionally characterized in insects. These enzymes are only expressed in the male antennae, and secreted into the lumen of the pheromone-sensitive sensilla. CCEs able to hydrolyze other odorants than sex pheromones, such as plant volatiles, have not been identified. Methodology: In Spodoptera littoralis, a major crop pest, a diversity of antennal CCEs has been previously identified. We have employed here a combination of molecular biology, biochemistry and electrophysiology approaches to functionally characterize an intracellular CCE, SlCXE10, whose predominant expression in the olfactory sensilla suggested a role in olfaction. A recombinant protein was produced using the baculovirus system and we tested its catabolic properties towards a plant volatile and the sex pheromone components. Conclusion: We showed that SlCXE10 could efficiently hydrolyze a green leaf volatile and to a lesser extent the sex pheromone components. The transcript level in male antennae was also strongly induced by exposure to this plant odorant. In antennae, SlCXE10 expression was associated with sensilla responding to the sex pheromones and to plant odours. These results suggest that a CCE-based intracellular metabolism of odorants could occur in insect antennae, in addition to the extracellular metabolism occurring within the sensillar lumen. This is the first functional characterization of an Odorant- Degrading Enzyme active towards a host plant volatile.

How we experience immersive virtual environments: the concept of presence and its measurement

This paper reviews the concept of presence in immersive virtual environments, the sense of being there signalled by people acting and responding realistically to virtual situations and events. We argue that presence is a unique phenomenon that must be distinguished from the degree of engagement, involvement in the portrayed environment. We argue that there are three necessary conditions for presence: the (a) consistent low latency sensorimotor loop between sensory data and proprioception; (b) statistical plausibility: images must be statistically plausible in relation to the probability distribution of images over natural scenes. A constraint on this plausibility is the level of immersion;(c) behaviour-response correlations: Presence may be enhanced and maintained over time by appropriate correlations between the state and behaviour of participants and responses within the environment, correlations that show appropriate responses to the activity of the participants. We conclude with a discussion of methods for assessing whether presence occurs, and in particular recommend the approach of comparison with ground truth and give some examples of this.