An fMRI study of parietal cortex involvement in the visual guidance of locomotion

Locomoting through the environment typically involves anticipating impending changes in heading trajectory in addition to maintaining the current direction of travel. We explored the neural systems involved in the “far road” and “near road” mechanisms proposed by Land and Horwood (1995) using simulated forward or backward travel where participants were required to gauge their current direction of travel (rather than directly control it). During forward egomotion, the distant road edges provided future path information, which participants used to improve their heading judgments. During backward egomotion, the road edges did not enhance performance because they no longer provided prospective information. This behavioral dissociation was reflected at the neural level, where only simulated forward travel increased activation in a region of the superior parietal lobe and the medial intraparietal sulcus. Providing only near road information during a forward heading judgment task resulted in activation in the motion complex. We propose a complementary role for the posterior parietal cortex and motion complex in detecting future path information and maintaining current lane positioning, respectively. (PsycINFO Database Record (c) 2010 APA, all rights reserved

Designing Tax Policy: Constraints and Objectives in an Open Economy

This paper is a non-technical discussion by an economist and lawyer, each with long international experience in taxation, of the constraints and objectives that in principle and practice shape tax policy design. After discussing the main factors traditionally taken into account by those charged with designing tax policy in any country – such as revenue, the costs of taxation, equity and fairness, administrability, and the effects of taxation on growth and other non-fiscal objectives – several additional important considerations associated with ‘globalization’ are then discussed with special attention to income taxes. The paper concludes with a brief reflection on how the ‘new world tax order’ in which countries must now develop their tax systems may perhaps develop over time

Visual anticipation of the future path : Predictive gaze and steering

Skillful behavior requires the anticipation of future action requirements. This is particularly true during high-speed locomotor steering where solely detecting and correcting current error is insufficient to produce smooth and accurate trajectories. Anticipating future steering requirements could be supported using "model-free" prospective signals from the scene ahead or might rely instead on model-based predictive control solutions. The present study generated conditions whereby the future steering trajectory was specified using a breadcrumb trail of waypoints, placed at regular intervals on the ground to create a predictable course (a repeated series of identical "S-bends"). The steering trajectories and gaze behavior relative to each waypoint were recorded for each participant (N = 16). To investigate the extent to which drivers predicted the location of future waypoints, "gaps" were included (20% of waypoints) whereby the next waypoint in the sequence did not appear. Gap location was varied relative to the S-bend inflection point to manipulate the chances that the next waypoint indicated a change in direction of the bend. Gaze patterns did indeed change according to gap location, suggesting that participants were sensitive to the underlying structure of the course and were predicting the future waypoint locations. The results demonstrate that gaze and steering both rely upon anticipation of the future path consistent with some form of internal model.Peer reviewe

The African Lungfish (\u3cem\u3eProtopterus dolloi\u3c/em\u3e): Ionoregulation and Osmoregulation in a Fish out of Water

Although urea production and metabolism in lungish have been thoroughly studied, we have little knowledge of how internal osmotic and electrolyte balance are controlled during estivation or in water. We tested the hypothesis that, compared with the body surface of teleosts, the slender African lungfish (Protopterus dolloi) body surface was relatively impermeable to water, Na+ and Cl- due to its greatly reduced gills. Accordingly, we measured the tritiated water (3H-H2O) flux in P. dolloi in water and during air exposure. In water, 3H-H2O efflux was comparable with the lowest measurements reported in freshwater teleosts, with a rate constant (K) of 17.6% body water h-1. Unidirectional ion fluxes, measured using 22Na+ and 36Cl-, indicated that Na+ and Cl- influx was more than 90% lower than values reported in most freshwater teleosts. During air exposure, a cocoon formed within 1 wk that completely covered the dorsolateral body surface. However, there were no disturbances to blood osmotic or ion (Na+, Cl-) balance, despite seven- to eightfold increases in plasma urea after 20 wk. Up to 13-fold increases in muscle urea (on a dry-weight basis) were the likely explanation for the 56% increase in muscle water content observed after 20 wk of air exposure. The possibility that muscle acted as a “water reservoir” during air exposure was supported by the 20% decline in body mass observed during subsequent reimmersion in water. This decline in body mass was equivalent to 28 mL water in a 100-g animal and was very close to the calculated net water gain (approximately 32 mL) observed during the 20-wk period of air exposure. Tritiated water and unidirectional ion fluxes on air-exposed lungfish revealed that the majority of water and ion exchange was via the ventral body surface at rates that were initially similar to aquatic rates. The 3H-H2O flux declined over time but increased upon reimmersion. We conclude that the slender lungfish body surface, including the gills, has relatively low permeability to water and ions but that the ventral surface is an important site of osmoregulation and ionoregulation. We further propose that an amphibian-like combination of ventral skin water and ion permeability, plus internal urea accumulation during air exposure, allows P. dolloi to extract water from its surroundings and to store water in the muscle when the water supply becomes limited

Drivers use active gaze to monitor waypoints during automated driving

Peer reviewe

Humans Use Predictive Gaze Strategies to Target Waypoints for Steering

A major unresolved question in understanding visually guided locomotion in humans is whether actions are driven solely by the immediately available optical information (model-free online control mechanisms), or whether internal models have a role in anticipating the future path. We designed two experiments to investigate this issue, measuring spontaneous gaze behaviour while steering, and predictive gaze behaviour when future path information was withheld. In Experiment 1 participants (N = 15) steered along a winding path with rich optic flow: gaze patterns were consistent with tracking waypoints on the future path 1–3 s ahead. In Experiment 2, participants (N = 12) followed a path presented only in the form of visual waypoints located on an otherwise featureless ground plane. New waypoints appeared periodically every 0.75 s and predictably 2 s ahead, except in 25% of the cases the waypoint at the expected location was not displayed. In these cases, there were always other visible waypoints for the participant to fixate, yet participants continued to make saccades to the empty, but predictable, waypoint locations (in line with internal models of the future path guiding gaze fixations). This would not be expected based upon existing model-free online steering control models, and strongly points to a need for models of steering control to include mechanisms for predictive gaze control that support anticipatory path following behaviours.A major unresolved question in understanding visually guided locomotion in humans is whether actions are driven solely by the immediately available optical information (model-free online control mechanisms), or whether internal models have a role in anticipating the future path. We designed two experiments to investigate this issue, measuring spontaneous gaze behaviour while steering, and predictive gaze behaviour when future path information was withheld. In Experiment 1 participants (N = 15) steered along a winding path with rich optic flow: gaze patterns were consistent with tracking waypoints on the future path 1–3 s ahead. In Experiment 2, participants (N = 12) followed a path presented only in the form of visual waypoints located on an otherwise featureless ground plane. New waypoints appeared periodically every 0.75 s and predictably 2 s ahead, except in 25% of the cases the waypoint at the expected location was not displayed. In these cases, there were always other visible waypoints for the participant to fixate, yet participants continued to make saccades to the empty, but predictable, waypoint locations (in line with internal models of the future path guiding gaze fixations). This would not be expected based upon existing model-free online steering control models, and strongly points to a need for models of steering control to include mechanisms for predictive gaze control that support anticipatory path following behaviours.Peer reviewe

Identification of Dictyostelium G_ɑ genes expressed during multicellular development

Guanine nucleotide-binding protein (G protein)-mediated signal transduction constitutes a common mechanism by which cells receive and respond to a diverse set of environmental signals. Many of the signals involved in the developmental life cycle of the slime mold Dictyostelium have been postulated to be transduced by such pathways and, in some cases, these pathways have been demonstrated to be dependent on specific G proteins. Using the polymerase chain reaction, we have identified two additional Dictyostelium G_ɑ genes, G_ɑ4 and G_ɑ5, that are developmentally regulated. Transcripts from both of these genes are primarily expressed during the multicellular stages of development, suggesting possible roles in cell differentiation or morphogenesis. The entire G_ɑ 4 gene was sequenced and found to encode a protein consisting of 345 amino acids. The G_ɑ4 subunit is homologous to other previously identified G_ɑ subunits, including the Dictyostelium Gɑ1 (43% identity) and G_ɑ2 (41% identity) subunits. However, the G_ɑ4 subunit contains some unusual sequence divergences in residues highly conserved among most eukaryotic G_ɑ subunits, suggesting that G_ɑ4 may be a member of another class of G_ɑ subunits

Hitting the target: Mathematical attainment in children is related to interceptive timing ability

Interceptive timing (IntT) is a fundamental ability underpinning numerous actions (e.g. ball catching), but its development and relationship with other cognitive functions remains poorly understood. Piaget (1955) suggested that children need to learn the physical rules that govern their environment before they can represent abstract concepts such as number and time. Thus, learning how objects move in space and time may underpin the development of related abstract representations (i.e. mathematics). To test this hypothesis, we captured objective measures of IntT in 309 primary school children (4-11 years), alongside ‘general motor skill’ and ‘national standardized academic attainment’ scores. Bayesian estimation showed that IntT (but not general motor capability) uniquely predicted mathematical ability even after controlling for age, reading and writing attainment. This finding highlights that interceptive timing is distinct from other motor skills with specificity in predicting childhood mathematical ability independent of other forms of attainment and motor capability

HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells

Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong persistence. Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations. Among these, the deletion of the UL/b’ domain is associated with loss of virulence. In a screen of UL/b’, we identified pUL135 as a protein responsible for the characteristic cytopathic effect of clinical HCMV strains that also protected from natural killer (NK) and T cell attack. pUL135 interacted directly with abl interactor 1 (ABI1) and ABI2 to recruit the WAVE2 regulatory complex to the plasma membrane, remodel the actin cytoskeleton and dramatically reduce the efficiency of immune synapse (IS) formation. An intimate association between F-actin filaments in target cells and the IS was dispelled by pUL135 expression. Thus, F-actin in target cells plays a critical role in synaptogenesis, and this can be exploited by pathogens to protect against cytotoxic immune effector cells. An independent interaction between pUL135 and talin disrupted cell contacts with the extracellular matrix

Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Secondary progressive multiple sclerosis, for which no satisfactory treatment presently exists, accounts for most of the disability in patients with multiple sclerosis. Simvastatin, which is widely used for treatment of vascular disease, with its excellent safety profile, has immunomodulatory and neuroprotective properties that could make it an appealing candidate drug for patients with secondary progressive multiple sclerosis. METHODS: We undertook a double-blind, controlled trial between Jan 28, 2008, and Nov 4, 2011, at three neuroscience centres in the UK. Patients aged 18-65 years with secondary progressive multiple sclerosis were randomly assigned (1:1), by a centralised web-based service with a block size of eight, to receive either 80 mg of simvastatin or placebo. Patients, treating physicians, and outcome assessors were masked to treatment allocation. The primary outcome was the annualised rate of whole-brain atrophy measured from serial volumetric MRI. Analyses were by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT00647348. FINDINGS: 140 participants were randomly assigned to receive either simvastatin (n=70) or placebo (n=70). The mean annualised atrophy rate was significantly lower in patients in the simvastatin group (0·288% per year [SD 0·521]) than in those in the placebo group (0·584% per year [0·498]). The adjusted difference in atrophy rate between groups was -0·254% per year (95% CI -0·422 to -0·087; p=0·003); a 43% reduction in annualised rate. Simvastatin was well tolerated, with no differences between the placebo and simvastatin groups in proportions of participants who had serious adverse events (14 [20%] vs nine [13%]). INTERPRETATION: High-dose simvastatin reduced the annualised rate of whole-brain atrophy compared with placebo, and was well tolerated and safe. These results support the advancement of this treatment to phase 3 testing. FUNDING: The Moulton Foundation [charity number 1109891], Berkeley Foundation [268369], the Multiple Sclerosis Trials Collaboration [1113598], the Rosetrees Trust [298582] and a personal contribution from A Pidgley, UK National Institute of Health Research (NIHR) University College London Hospitals/UCL Biomedical Research Centres funding scheme