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Vale, N.

Publications and source records attributed to Vale, N..

2 recordsLinked to original sources

Divisive attenuation based on noisy sensorimotor predictions accounts for excess variability in self-touch

When one part of the body exerts force on another, the resulting tactile sensation is perceived as weaker than when the same force is applied by an external agent. This phenomenon has been studied using a force matching task, in which observers are first exposed to an external force on a passive finger and then instructed to reproduce the sensation by directly pressing on the passive finger with a finger of the other hand: healthy participants consistently exceed the original force level. However, this exaggeration of the target force is not observed if the observer generates the matching force indirectly, by adjusting a joystick or slider that controls the force output of a motor. Here we present the first detailed computational account of the processes leading to exaggeration of target forces in the force matching task, incorporating attenuation of sensory signals based on motor predictions. The model elucidates previously unappreciated contributions of multiple sources of noise, including memory noise, in determining matching force output, and shows that quantifying attenuation as the discrepancy between direct and indirect self-generated forces isolates its predictive component. Our computational account makes the prediction that attenuated sensations will display greater trial-to-trial variability than unattenuated ones, because they incorporate additional noise from motor prediction. Quantitative model fitting of new and existing force matching data confirmed the prediction of excess variability in self-generated forces and provided evidence for a divisive rather than subtractive mechanism of attenuation, while highlighting its predictive nature. NEW & NOTEWORTHYWe formulate a detailed computational account of sensory attenuation in force matching tasks that disambiguates contributions of perceptual, memory and prediction noise in order to isolate a pure measure of attenuation strength. Analysis of data from nearly 500 participants shows that attenuated sensations display increased trial-to-trial variability, consistent with incorporating additional noise inherent to motor prediction. These results support a divisive - rather than subtractive - reduction in the sensation of self-generated forces based on predicted reafference.

neuroscience↗

Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

Chronic infections with the flatworm parasites Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium are classified as group 1 biological carcinogens, i.e. definitive causes of cancer. In addition, we reported findings that support the inclusion of Opisthorchis felineus in this list of biological carcinogens. By contrast, infections with close phylogenetic relatives including Fasciola hepatica have not been associated with carcinogenesis. Earlier reports revealed of oxysterol metabolites of Opisthorchis liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here we employed liquid chromatography-mass spectrometry (LC-MS/MS) to investigate, compare and contrast spectrograms of soluble extracts from F. hepatica adult worms from bile ducts of cattle with those from O. viverrini and O. felineus from experimentally-infected hamsters. F. hepatica displayed a complex spectrophotometric profile. F. hepatica and Opisthorchis spp. shared several common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of these Opisthorchis species included far fewer compounds than F. hepatica. These findings support the postulate that oxysterol-like metabolites of parasite origin can initiate carcinogenesis and they point to a molecular basis for the inconsistencies among major groups of liver flukes concerning infection-induced malignancy.\n\nAuthor SummarySeveral species of trematodes are parasites of the human hepatobiliary tract. Infection with two of these flukes, Clonorchis sinsensis and Opisthorchis viverrini, fresh water fish-borne parasites that occur in East Asia is classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC), i.e. definitive causes of cancer in humans. By contrast, infection with a different liver fluke, Fasciola hepatica, does not lead to malignant transformation of the biliary tract. Given the close phylogeny of all three parasites, this difference in carcinogenicity is intriguing and, if explained, likely of value in novel therapeutic approaches. The importance of the current findings is informative because they present a mass spectrometric analysis and catalog of the similarities and differences between fluke of the genus Opisthorchis and F. hepatica, potentially identifying carcinogenic metabolites of liver fluke origin. These metabolites can be expected to provide deeper understanding of helminth infection induced malignancy.

cancer biology↗