Neglect-Like Effects on Drawing Symmetry Induced by Adaptation to a Laterally Asymmetric Visuomotor Delay

In daily interactions, our sensorimotor system accounts for spatial and temporal discrepancies between the senses. Functional lateralization between hemispheres causes differences in attention and in the control of action across the left and right workspaces. In addition, differences in transmission delays between modalities affect movement control and internal representations. Studies on motor impairments such as hemispatial neglect syndrome suggested a link between lateral spatial biases and temporal processing. To understand this link, we computationally modeled and experimentally validated the effect of laterally asymmetric delay in visual feedback on motor learning and its transfer to the control of drawing movements without visual feedback. In the behavioral experiments, we asked healthy participants to perform lateral reaching movements while adapting to delayed visual feedback in either left, right, or both workspaces. We found that the adaptation transferred to blind drawing and caused movement elongation, which is consistent with a state representation of the delay. However, the pattern of the spatial effect varied between conditions: whereas adaptation to delay in only the left workspace or in the whole workspace caused selective leftward elongation, adaptation to delay in only the right workspace caused drawing elongation in both directions. We simulated arm movements according to different models of perceptual and motor spatial asymmetry in the representation of delay and found that the best model that accounts for our results combines both perceptual and motor asymmetry between the hemispheres. These results provide direct evidence for an asymmetrical processing of delayed visual feedback that is associated with both perceptual and motor biases that are similar to those observed in hemispatial neglect syndrome

The acquisition of mechano-electrical transducer current adaptation in auditory hair cells requires myosin VI

Mutations in Myo6, the gene encoding the (F-actin) minus end-directed unconventional myosin, myosin VI, cause hereditary deafness in mice (Snell's waltzer) and humans. In the sensory hair cells of the cochlea, myosin VI is expressed in the cell bodies and along the stereocilia that project from the cells’ apical surface. It is required for maintaining the structural integrity of the mechanosensitive hair bundles formed by the stereocilia. In this study we investigate whether myosin VI contributes to mechano-electrical transduction. We report that Ca²+-dependent adaptation of the mechano-electrical transducer (MET) current, which serves to keep the transduction apparatus operating within its most sensitive range, is absent in outer and inner hair cells from homozygous Snell's waltzer mutant mice, which fail to express myosin VI. The operating range of the MET channels is also abnormal in the mutants, resulting in the absence of a resting MET current. We found that cadherin 23, a component of the hair bundle's transient lateral links, fails to be downregulated along the length of the stereocilia in maturing Myo6 mutant mice. MET currents of heterozygous littermates appear normal. We propose that myosin VI, by removing key molecules from developing hair bundles, is required for the development of the MET apparatus and its Ca²+-dependent adaptation

Human Muscle Progenitor Cells Overexpressing Neurotrophic Factors Improve Neuronal Regeneration in a Sciatic Nerve Injury Mouse Model

The peripheral nervous system has an intrinsic ability to regenerate after injury. However, this process is slow, incomplete, and often accompanied by disturbing motor and sensory consequences. Sciatic nerve injury (SNI), which is the most common model for studying peripheral nerve injury, is characterized by damage to both motor and sensory fibers. The main goal of this study is to examine the feasibility of administration of human muscle progenitor cells (hMPCs) overexpressing neurotrophic factor (NTF) genes, known to protect peripheral neurons and enhance axon regeneration and functional recovery, to ameliorate motoric and sensory deficits in SNI mouse model. To this end, hMPCs were isolated from a human muscle biopsy, and manipulated to ectopically express brain-derived neurotrophic factor (BDNF), glial-cell-line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1). These hMPC-NTF were transplanted into the gastrocnemius muscle of mice after SNI, and motor and sensory functions of the mice were assessed using the CatWalk XT system and the hot plate test. ELISA analysis showed that genetically manipulated hMPC-NTF express significant amounts of BDNF, GDNF, VEGF, or IGF-1. Transplantation of 3 × 106 hMPC-NTF was shown to improve motor function and gait pattern in mice following SNI surgery, as indicated by the CatWalk XT system 7 days post-surgery. Moreover, using the hot-plate test, performed 6 days after surgery, the treated mice showed less sensory deficits, indicating a palliative effect of the treatment. ELISA analysis following transplantation demonstrated increased NTF expression levels in the gastrocnemius muscle of the treated mice, reinforcing the hypothesis that the observed positive effect was due to the transplantation of the genetically manipulated hMPC-NTF. These results show that genetically modified hMPC can alleviate both motoric and sensory deficits of SNI. The use of hMPC-NTF demonstrates the feasibility of a treatment paradigm, which may lead to rapid, high-quality healing of damaged peripheral nerves due to administration of hMPC. Our approach suggests a possible clinical application for the treatment of peripheral nerve injury

In vivo percutaneous penetration/absorption : Sponsored by the American Association of Pharmaceutical Scientist, U.S. Food and Drug Administration, American Academy of Dermatology, Skin Pharmacology Society and the U.S. Army Environmental Hygiene Agency May 1-3, 1989, Washington, DC

This workshop, `In Vivo Percutaneous Penetration/Absorption' was held in Washington, DC, on May 1-3, 1989. The first workshop in this series, `In Vitro Percutaneous Penetration', took place in November 1986 (the report of this earlier meeting was published in Pharmaceutical Research, 4 (1987) 265-267). The objectives of the workshop were to review the relevant literature and to address in detail: (1) In vivo percutaneous penetration/absorption methodology; (2) The characteristics of dosage forms designed for application to the skin; (3) Critical factors controlling in vivo drug transport into and across the skin; (4) The use of models in the assessment and evaluation of in vivo percutaneous penetration/absorption; and (5) Bioavailability/bioequivalence considerations for topical drug products. Scientific knowledge and technology are rapidly evolving in the topical and transdermal drug products area. This report focuses on the methodologies available for the measurement of percutaneous penetration in vivo; each scientific approach is discussed briefly followed by advantages and disadvantages of the methodology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29180/1/0000227.pd

Multifunctional crop trait ontology for breeders' data: field book, annotation, data discovery and semantic enrichment of the literature

The ‘Crop Ontology’ database we describe provides a controlled vocabulary for several economically important crops. It facilitates data integration and discovery from global databases and digital literature. This allows researchers to exploit comparative phenotypic and genotypic information of crops to elucidate functional aspects of traits

Whole organisms or pure compounds? entourage effect versus drug specificity

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.2019-07-3