Mental Rotation of Digitally-Rendered Haptic Objects by the Visually-Impaired.

In the event of visual impairment or blindness, information from other intact senses can be used as substitutes to retrain (and in extremis replace) visual functions. Abilities including reading, mental representation of objects and spatial navigation can be performed using tactile information. Current technologies can convey a restricted library of stimuli, either because they depend on real objects or renderings with low resolution layouts. Digital haptic technologies can overcome such limitations. The applicability of this technology was previously demonstrated in sighted participants. Here, we reasoned that visually-impaired and blind participants can create mental representations of letters presented haptically in normal and mirror-reversed form without the use of any visual information, and mentally manipulate such representations. Visually-impaired and blind volunteers were blindfolded and trained on the haptic tablet with two letters (either L and P or F and G). During testing, they haptically explored on any trial one of the four letters presented at 0°, 90°, 180°, or 270° rotation from upright and indicated if the letter was either in a normal or mirror-reversed form. Rotation angle impacted performance; greater deviation from 0° resulted in greater impairment for trained and untrained normal letters, consistent with mental rotation of these haptically-rendered objects. Performance was also generally less accurate with mirror-reversed stimuli, which was not affected by rotation angle. Our findings demonstrate, for the first time, the suitability of a digital haptic technology in the blind and visually-impaired. Classic devices remain limited in their accessibility and in the flexibility of their applications. We show that mental representations can be generated and manipulated using digital haptic technology. This technology may thus offer an innovative solution to the mitigation of impairments in the visually-impaired, and to the training of skills dependent on mental representations and their spatial manipulation

Mental Rotation of Digitally-Rendered Haptic Objects.

Sensory substitution is an effective means to rehabilitate many visual functions after visual impairment or blindness. Tactile information, for example, is particularly useful for functions such as reading, mental rotation, shape recognition, or exploration of space. Extant haptic technologies typically rely on real physical objects or pneumatically driven renderings and thus provide a limited library of stimuli to users. New developments in digital haptic technologies now make it possible to actively simulate an unprecedented range of tactile sensations. We provide a proof-of-concept for a new type of technology (hereafter haptic tablet) that renders haptic feedback by modulating the friction of a flat screen through ultrasonic vibrations of varying shapes to create the sensation of texture when the screen is actively explored. We reasoned that participants should be able to create mental representations of letters presented in normal and mirror-reversed haptic form without the use of any visual information and to manipulate such representations in a mental rotation task. Healthy sighted, blindfolded volunteers were trained to discriminate between two letters (either L and P, or F and G; counterbalanced across participants) on a haptic tablet. They then tactually explored all four letters in normal or mirror-reversed form at different rotations (0°, 90°, 180°, and 270°) and indicated letter form (i.e., normal or mirror-reversed) by pressing one of two mouse buttons. We observed the typical effect of rotation angle on object discrimination performance (i.e., greater deviation from 0° resulted in worse performance) for trained letters, consistent with mental rotation of these haptically-rendered objects. We likewise observed generally slower and less accurate performance with mirror-reversed compared to prototypically oriented stimuli. Our findings extend existing research in multisensory object recognition by indicating that a new technology simulating active haptic feedback can support the generation and spatial manipulation of mental representations of objects. Thus, such haptic tablets can offer a new avenue to mitigate visual impairments and train skills dependent on mental object-based representations and their spatial manipulation

Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells

Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines compose a class of compounds that target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo[1,2-a]pyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo[1,2-a]pyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo[1,2-a]pyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical–genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure–activity relationships