Perceptual Coupling Based on Depth and Motion Cues in Stereovision-Impaired Subjects.

When an object is partially occluded, the different parts of the object have to be perceptually coupled. Cues that can be used for perceptual coupling are, for instance, depth ordering and visual motion information. In subjects with impaired stereovision, the brain is less able to use stereoscopic depth cues, making them more reliant on other cues. Therefore, our hypothesis is that stereovision-impaired subjects have stronger motion coupling than stereoscopic subjects. We compared perceptual coupling in 8 stereoscopic and 10 stereovision-impaired subjects, using random moving dot patterns that defined an ambiguous rotating cylinder and a coaxially presented nonambiguous half cylinder. Our results show that, whereas stereoscopic subjects exhibit significant coupling in the far plane, stereovision-impaired subjects show no coupling and under our conditions also no stronger motion coupling than stereoscopic subjects.

Opto-locomotor reflexes of mice to reverse-phi stimuli.

In a reverse-phi stimulus, the contrast luminance of moving dots is reversed each displacement step. Under those conditions, the direction of the moving dots is perceived in the direction opposite of the displacement direction of the dots. In this study, we investigate if mice respond oppositely to phi and reverse-phi stimuli. Mice ran head-fixed on a Styrofoam ball floating on pressurized air at the center of a large dome. We projected random dot patterns that were displaced rightward or leftward, using either a phi or a reverse-phi stimulus. For phi stimuli, changes in direction caused the mice to reflexively compensate and adjust their running direction in the direction of the displaced pattern. We show that for reverse-phi stimuli mice compensate in the direction opposite to the displacement direction of the dots, in accordance with the perceived direction of displacement in humans for reverse-phi stimuli.

Monocular and binocular opto-locomotor reflex biases for random dot motion in mice.

We investigated the relationship between eyes receiving visual input of large field translating random dot motion and subsequent reflexive changes in running direction in mice. The animals were head-fixed running on a Styrofoam ball and the opto-locomotor reflex (OLR) was measured in response to 2 s of dots patterns moving horizontally to the left or right. We measured the OLR in conditions with both eyes open (binocular) and one eye closed (monocular). When we covered the right or left eye in the monocular condition, we found reflexive behavior to be delayed for a few hundred milliseconds to leftward or rightward motion, respectively. After this delay, the bias disappeared and reflexive behavior was similar to responses to motion under binocular conditions. These results might be explained by different contributions of subcortical and cortical visual motion processing pathways to the OLR. Furthermore, we found no evidence for nonlinear interactions between the two eyes, because the sum of the OLR of the two monocular conditions was equal in amplitude and temporal characteristics to the OLR under binocular conditions.

Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disability.

BACKGROUND: MicroRNAs (miRNAs) are non-coding gene transcripts involved in post-transcriptional regulation of genes. Recent studies identified miRNAs as important regulators of learning and memory in model organisms. So far, no mutations in specific miRNA genes have been associated with impaired cognitive functions. METHODS AND RESULTS: In three sibs and two unrelated patients with intellectual disability (ID), overlapping 1p21.3 deletions were detected by genome-wide array analysis. The shortest region of overlap included dihydropyrimidine dehydrogenase (DPYD) and microRNA 137 (MIR137). DPYD is involved in autosomal recessive dihydropyrimidine dehydrogenase deficiency. Hemizygous DPYD deletions were previously suggested to contribute to a phenotype with autism spectrum disorder and speech delay. Interestingly, the mature microRNA transcript microRNA-137 (miR-137) was recently shown to be involved in modulating neurogenesis in adult murine neuronal stem cells. Therefore, this study investigated the possible involvement of MIR137 in the 1p21.3-deletion phenotype. The patients displayed a significantly decreased expression of both precursor and mature miR-137 levels, as well as significantly increased expression of the validated downstream targets microphthalmia-associated transcription factor (MITF) and Enhancer of Zeste, Drosophila, Homologue 2 (EZH2), and the newly identified target Kruppel-like factor 4 (KLF4). The study also demonstrated significant enrichment of miR-137 at the synapses of cortical and hippocampal neurons, suggesting a role of miR-137 in regulating local synaptic protein synthesis machinery. CONCLUSIONS: This study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA. A local effect at the synapse might be responsible.

A new use for old drugs: identifying compounds with an anti-obesity effect using a high through-put semi-automated Caenorhabditis elegans screening platform.

Obesity is one of the most common global health problems for all age groups with obese people at risk of a variety of associated health complications. Consequently, there is a need to develop new therapies that lower body fat without the side effects. However, obesity is a complex and systemic disease, so that in vitro results are not easily translatable to clinical situations. A promising way to circumnavigate these issues is to reposition already approved drugs for new treatments, enabling a more streamlined drug discovery process due to the availability of pre-existing pharmacological and toxicological datasets. Chemical libraries, such as the Prestwick Chemical Library of 1200 FDA approved drugs, are available for this purpose. We have developed a simple semi-automated whole-organism approach to screening the Prestwick Chemical Library for those compounds which reduce fat content using the model organism Caenorhabditis elegans. Our whole-organism approach to high-throughput screening identified 9 "lead" compounds that reduced fat within 2 weeks in the model. Further screening and analysis provided 4 "hit" compounds (Midodrine, Vinpocetine, Fenoprofen and Lamivudine) that showed significant promise as drugs to reduce fat levels. The effects of these candidates were found to further reduce fat content in nematodes where an nhr-49/PPAR mutation resulted in "overweight" worms. Upon unblinding the "hit" compounds, they were found to have recently been shown to have anti-obesity effects in mammalian models too. In developing a whole-animal chemical screen to identify pharmacological agents as potential anti-obesity compounds, we demonstrate how chemical libraries can be rapidly and relatively cheaply profiled for active hits. Using the nematode Caenorhabditis elegans thus enables drugs to be assessed for applicability in humans and provides a new incentive to explore drug repurposing as a feasible and efficient way to identify new anti-obesity compounds.