121 research outputs found

    Mapping Proprioception across a 2D Horizontal Workspace

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    Relatively few studies have been reported that document how proprioception varies across the workspace of the human arm. Here we examined proprioceptive function across a horizontal planar workspace, using a new method that avoids active movement and interactions with other sensory modalities. We systematically mapped both proprioceptive acuity (sensitivity to hand position change) and bias (perceived location of the hand), across a horizontal-plane 2D workspace. Proprioception of both the left and right arms was tested at nine workspace locations and in 2 orthogonal directions (left-right and forwards-backwards). Subjects made repeated judgments about the position of their hand with respect to a remembered proprioceptive reference position, while grasping the handle of a robotic linkage that passively moved their hand to each judgement location. To rule out the possibility that the memory component of the proprioceptive testing procedure may have influenced our results, we repeated the procedure in a second experiment using a persistent visual reference position. Both methods resulted in qualitatively similar findings. Proprioception is not uniform across the workspace. Acuity was greater for limb configurations in which the hand was closer to the body, and was greater in a forward-backward direction than in a left-right direction. A robust difference in proprioceptive bias was observed across both experiments. At all workspace locations, the left hand was perceived to be to the left of its actual position, and the right hand was perceived to be to the right of its actual position. Finally, bias was smaller for hand positions closer to the body. The results of this study provide a systematic map of proprioceptive acuity and bias across the workspace of the limb that may be used to augment computational models of sensory-motor control, and to inform clinical assessment of sensory function in patients with sensory-motor deficits

    High motor variability in DYT1 dystonia is associated with impaired visuomotor adaptation.

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    For the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. Reaching movements in the symptomatic arm of 10 patients with DYT1 dystonia and 12 age-matched controls were captured using a robotic manipulandum and features of motor variability were extracted. Given that task-relevant variability and sensorimotor adaptation are related in health, markers of variability were then examined for any co-variance with performance indicators during an error-based learning visuomotor adaptation task. First, we confirmed that motor variability on a trial-by-trial basis was selectively increased in the homogenous and prototypical dystonic disorder DYT1 dystonia. Second, high baseline variability predicted poor performance in the subsequent visuomotor adaptation task offering insight into the rules which appear to govern dystonic motor control. The potential mechanisms behind increased motor variability and its corresponding implications for the rehabilitation of patients with DYT1 dystonia are highlighted

    Impact of Climate Change on Voltinism and Prospective Diapause Induction of a Global Pest Insect – Cydia pomonella (L.)

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    Global warming will lead to earlier beginnings and prolongation of growing seasons in temperate regions and will have pronounced effects on phenology and life-history adaptation in many species. These changes were not easy to simulate for actual phenologies because of the rudimentary temporal (season) and spatial (regional) resolution of climate model projections. We investigate the effect of climate change on the regional incidence of a pest insect with nearly worldwide distribution and very high potential for adaptation to season length and temperature – the Codling Moth, Cydia pomonella. Seasonal and regional climate change signals were downscaled to the hourly temporal scale of a pest phenology model and the spatial scale of pest habitats using a stochastic weather generator operating at daily scale in combination with a re-sampling approach for simulation of hourly weather data. Under future conditions of increased temperatures (2045–2074), the present risk of below 20% for a pronounced second generation (peak larval emergence) in Switzerland will increase to 70–100%. The risk of an additional third generation will increase from presently 0–2% to 100%. We identified a significant two-week shift to earlier dates in phenological stages, such as overwintering adult flight. The relative extent (magnitude) of first generation pupae and all later stages will significantly increase. The presence of first generation pupae and later stages will be prolonged. A significant decrease in the length of overlap of first and second generation larval emergence was identified. Such shifts in phenology may induce changes in life-history traits regulating the life cycle. An accordingly life-history adaptation in photoperiodic diapause induction to shorter day-length is expected and would thereby even more increase the risk of an additional generation. With respect to Codling Moth management, the shifts in phenology and voltinism projected here will require adaptations of plant protection strategies to maintain their sustainability

    Compensation for Changing Motor Uncertainty

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    When movement outcome differs consistently from the intended movement, errors are used to correct subsequent movements (e.g., adaptation to displacing prisms or force fields) by updating an internal model of motor and/or sensory systems. Here, we examine changes to an internal model of the motor system under changes in the variance structure of movement errors lacking an overall bias. We introduced a horizontal visuomotor perturbation to change the statistical distribution of movement errors anisotropically, while monetary gains/losses were awarded based on movement outcomes. We derive predictions for simulated movement planners, each differing in its internal model of the motor system. We find that humans optimally respond to the overall change in error magnitude, but ignore the anisotropy of the error distribution. Through comparison with simulated movement planners, we found that aimpoints corresponded quantitatively to an ideal movement planner that updates a strictly isotropic (circular) internal model of the error distribution. Aimpoints were planned in a manner that ignored the direction-dependence of error magnitudes, despite the continuous availability of unambiguous information regarding the anisotropic distribution of actual motor errors

    Interstitial lung disease in children - genetic background and associated phenotypes

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    Interstitial lung disease in children represents a group of rare chronic respiratory disorders. There is growing evidence that mutations in the surfactant protein C gene play a role in the pathogenesis of certain forms of pediatric interstitial lung disease. Recently, mutations in the ABCA3 transporter were found as an underlying cause of fatal respiratory failure in neonates without surfactant protein B deficiency. Especially in familiar cases or in children of consanguineous parents, genetic diagnosis provides an useful tool to identify the underlying etiology of interstitial lung disease. The aim of this review is to summarize and to describe in detail the clinical features of hereditary interstitial lung disease in children. The knowledge of gene variants and associated phenotypes is crucial to identify relevant patients in clinical practice

    The Glasgow Outcome Scale -- 40 years of application and refinement

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    The Glasgow Outcome Scale (GOS) was first published in 1975 by Bryan Jennett and Michael Bond. With over 4,000 citations to the original paper, it is the most highly cited outcome measure in studies of brain injury and the second most-cited paper in clinical neurosurgery. The original GOS and the subsequently developed extended GOS (GOSE) are recommended by several national bodies as the outcome measure for major trauma and for head injury. The enduring appeal of the GOS is linked to its simplicity, short administration time, reliability and validity, stability, flexibility of administration (face-to-face, over the telephone and by post), cost-free availability and ease of access. These benefits apply to other derivatives of the scale, including the Glasgow Outcome at Discharge Scale (GODS) and the GOS paediatric revision. The GOS was devised to provide an overview of outcome and to focus on social recovery. Since the initial development of the GOS, there has been an increasing focus on the multidimensional nature of outcome after head injury. This Review charts the development of the GOS, its refinement and usage over the past 40 years, and considers its current and future roles in developing an understanding of brain injury

    Lung epithelial stem cells and their niches : Fgf10 takes center stage

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    Throughout life adult animals crucially depend on stem cell populations to maintain and repair their tissues to ensure life-long organ function. Stem cells are characterized by their capacity to extensively self-renew and give rise to one or more differentiated cell types. These powerful stem cell properties are key to meet the changing demand for tissue replacement during normal lung homeostasis and regeneration after lung injury. Great strides have been made over the last few years to identify and characterize lung epithelial stem cells as well as their lineage relationships. Unfortunately, knowledge on what regulates the behavior and fate specification of lung epithelial stem cells is still limited, but involves communication with their microenvironment or niche, a local tissue environment that hosts and influences the behaviors or characteristics of stem cells and that comprises other cell types and extracellular matrix. As such, an intimate and dynamic epithelial-mesenchymal cross-talk, which is also essential during lung development, is required for normal homeostasis and to mount an appropriate regenerative response after lung injury. Fibroblast growth factor 10 (Fgf10) signaling in particular seems to be a well-conserved signaling pathway governing epithelial-mesenchymal interactions during lung development as well as between different adult lung epithelial stem cells and their niches. On the other hand, disruption of these reciprocal interactions leads to a dysfunctional epithelial stem cell-niche unit, which may culminate in chronic lung diseases such as chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF)

    Integrated multi-omics analyses reveal the pleiotropic nature of the control of gene expression by Puf3p

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    The PUF family of RNA-binding proteins regulate gene expression post-transcriptionally. Saccharomyces cerevisiae Puf3p is characterised as binding nuclear-encoded mRNAs specifying mitochondrial proteins. Extensive studies of its regulation of COX17 demonstrate its role in mRNA decay. Using integrated genome-wide approaches we define an expanded set of Puf3p target mRNAs and quantitatively assessed the global impact of loss of PUF3 on gene expression using mRNA and polysome profiling and quantitative proteomics. In agreement with prior studies, our sequencing of affinity-purified Puf3-TAP associated mRNAs (RIP-seq) identified mRNAs encoding mitochondrially-targeted proteins. Additionally, we also found 720  new mRNA targets that predominantly encode proteins that enter the nucleus. Comparing transcript levels in wild-type and puf3∆ cells revealed that only a small fraction of mRNA levels alter, suggesting Puf3p determines mRNA stability for only a limited subset of its target mRNAs. Finally, proteomic and translatomic studies suggest that loss of Puf3p has widespread, but modest, impact on mRNA translation. Taken together our integrated multi-omics data point to multiple classes of Puf3p targets, which display coherent post-transcriptional regulatory properties and suggest Puf3p plays a broad, but nuanced, role in the fine-tuning of gene expression

    A common copy-number breakpoint of ERBB2 amplification in breast cancer colocalizes with a complex block of segmental duplications

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