Plasticity of the cortical representation of finger extensors induced by paired associative stimulation

This dissertation first explored associative plasticity of the human motor cortical representation with the use of noninvasive transcranial magnetic stimulation (TMS) paired with peripheral electrical stimulation. Paired Associative Stimulation (PAS) has grown in popularity because of its potential clinical applications. PAS techniques are used in combination with electromyography (EMG) measurements to study cortical excitability and features of hand movement. This work focuses on a cohesive approach to answer central questions about: the ideal mechanism to facilitate cortical plasticity via PAS, the interaction between the behavior performed and type of stimulation delivered to the targeted cortical network and the effects of PAS, the interaction between interstimulus timing, stimulus timing during movement and the translation of these effects into measurable changes starting from neurophysiological changes and ending up with the behavioral modulation of hand movement. First the role of interstimulus timing and intracortical facilitation on modulation of cortical excitability is explored in the extrinsic hand muscles by showing that PAS can be conditioned by these facilitatory intracortical networks. Using standard indirect approaches utilizing peripheral EMG measures and novel virtual reality (VR) environments, a graded excitability response is shown for the PAS technique and illustrates that interactions of PAS with voluntary movements impacts the degree as well as the state of cortical excitability. Rules governing the interactions of brain stimulation techniques and motor learning are important because brain stimulation techniques can be used to modify and improve neuro motor adaptation and skill learning with great potential for clinical applications such as facilitation of recovery after stroke. PAS provides us with a unique opportunity to study the rules of plasticity at a systems level, which is a combination of synaptic and non-synaptic (metaplastic) changes. Finally, it is shown that changes in cortical excitability may help modulate certain neurophysiological and clinical features of hand function in a pair of patients with chronic stroke in a pilot study. As expected, stroke patients exhibited a smaller degree of excitability increase. It is demonstrated that sessions of intense training with PAS in a VR environment induces significant neuroplastic changes in the sensorimotor cortex. Explicitly, VR based PAS facilitates corticospinal excitability in the ipsilesional sensorimotor cortex. As a result, this dissertation provides a new methodological and technical framework to condition the standard PAS paradigm to engage other intracortical networks. It also shows how PAS can be used to affect motor learning and the role of state of cortical excitation in induction of homeostatic or non-homeostatic plasticity for patients with neurological and neuromuscular impairments for example stroke plus the potential behavioral consequences of PAS in human motor cortex to facilitate functional recovery of hand function

Why is productivity slowing down?

The recent decline in aggregate labor productivity growth in leading economies has been widely described as a puzzle, even a paradox, leading to extensive research into possible explanations. Our review confirms the magnitude of the slowdown and finds that it is largely driven by a decline in total factor productivity and capital deepening. Disaggregation reveals that a significant part of the slowdown is due to sectors that experienced the large benefits from ICTs in the previous period, and that an increasing gap between frontier and laggard firms suggests slower technology diffusion and increasing misallocation of factors. We evaluate explanations that attempt to reconcile the paradox of slowing productivity growth and technological change, including mismeasurement, implementation lags for technologies, and creative destruction processes

The genome of the yellow potato cyst nematode, Globodera rostochiensis, reveals insights into the basis of parasitism and virulence

BACKGROUND: The yellow potato cyst nematode, Globodera rostochiensis, is a devastating plant pathogen of global economic importance. This biotrophic parasite secretes effectors from pharyngeal glands, some of which were acquired by horizontal gene transfer, to manipulate host processes and promote parasitism. G. rostochiensis is classified into pathotypes with different plant resistance-breaking phenotypes. RESULTS: We generate a high quality genome assembly for G. rostochiensis pathotype Ro1, identify putative effectors and horizontal gene transfer events, map gene expression through the life cycle focusing on key parasitic transitions and sequence the genomes of eight populations including four additional pathotypes to identify variation. Horizontal gene transfer contributes 3.5 % of the predicted genes, of which approximately 8.5 % are deployed as effectors. Over one-third of all effector genes are clustered in 21 putative ‘effector islands’ in the genome. We identify a dorsal gland promoter element motif (termed DOG Box) present upstream in representatives from 26 out of 28 dorsal gland effector families, and predict a putative effector superset associated with this motif. We validate gland cell expression in two novel genes by in situ hybridisation and catalogue dorsal gland promoter element-containing effectors from available cyst nematode genomes. Comparison of effector diversity between pathotypes highlights correlation with plant resistance-breaking. CONCLUSIONS: These G. rostochiensis genome resources will facilitate major advances in understanding nematode plant-parasitism. Dorsal gland promoter element-containing effectors are at the front line of the evolutionary arms race between plant and parasite and the ability to predict gland cell expression a priori promises rapid advances in understanding their roles and mechanisms of action.SE-vdA is supported by BBSRC grant BB/M014207/1. Sequencing was funded by BBSRC grant BB/F000642/1 to the University of Leeds and grant BB/F00334X/1 to the Wellcome Trust Sanger Institute). DRL was supported by a fellowship from The James Hutton Institute and the School of Biological Sciences, University of Edinburgh. GK was supported by a BBSRC PhD studentship. The James Hutton Institute receives funding from the Scottish Government. JAC and NEH are supported by the Wellcome Trust through its core funding of the Wellcome Trust Sanger Institute (grant 098051). This work was also supported by funding from the Canadian Safety and Security Program, project number CRTI09_462RD

Determining sectoral and regional sensitivity to climate and socio-economic change in Europe using impact response surfaces

Responses to future changes in climatic and socio-economic conditions can be expected to vary between sectors and regions, reflecting differential sensitivity to these highly uncertain factors. A sensitivity analysis was conducted using a suite of impact models (for health, agriculture, biodiversity, land use, floods and forestry) across Europe with respect to changes in key climate and socio-economic variables. Depending on the indicators, aggregated grid or indicative site results are reported for eight rectangular sub-regions that together span Europe from northern Finland to southern Spain and from western Ireland to the Baltic States and eastern Mediterranean, each plotted as scenario-neutral impact response surfaces (IRSs). These depict the modelled behaviour of an impact variable in response to changes in two key explanatory variables. To our knowledge, this is the first time the IRS approach has been applied to changes in socio-economic drivers and over such large regions. The British Isles region showed the smallest sensitivity to both temperature and precipitation, whereas Central Europe showed the strongest responses to temperature and Eastern Europe to precipitation. Across the regions, sensitivity to temperature was lowest for the two indicators of river discharge and highest for Norway spruce productivity. Sensitivity to precipitation was lowest for intensive agricultural land use, maize and potato yields and Scots pine productivity, and highest for Norway spruce productivity. Under future climate projections, North-eastern Europe showed increases in yields of all crops and productivity of all tree species, whereas Central and East Europe showed declines. River discharge indicators and forest productivity (except Holm oak) were projected to decline over southern European regions. Responses were more sensitive to socio-economic than to climate drivers for some impact indicators, as demonstrated for heat-related mortality, coastal flooding and land use

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Genome annotation. (XLSX 9 kb

Why is productivity slowing down?

We review recent research on the slowdown of labor productivity and examine the contribution of different explanations to this decline. Comparing the post-2005 period with the preceding decade for five advanced economies, we seek to explain a slowdown of 0.8 to 1.8pp. We trace most of this to lower contributions of TFP and capital deepening, with manufacturing accounting for the biggest sectoral share of the slowdown. No single explanation accounts for the slowdown, but we have identified a combination of factors which, taken together, accounts for much of what has been observed. In the countries we have studied, these are mismeasurement, a decline in the contribution of capital per worker, lower spillovers from the growth of intangible capital, the slowdown in trade, and a lower growth of allocative efficiency. Sectoral reallocation and a lower contribution of human capital may also have played a role in some countries. In addition to our quantitative assessment of explanations for the slowdown, we qualitatively assess other explanations, including whether productivity growth may be declining due to innovation slowing down

Robotically facilitated virtual rehabilitation of arm transport integrated with finger movement in persons with hemiparesis

Abstract Background Recovery of upper extremity function is particularly recalcitrant to successful rehabilitation. Robotic-assisted arm training devices integrated with virtual targets or complex virtual reality gaming simulations are being developed to deal with this problem. Neural control mechanisms indicate that reaching and hand-object manipulation are interdependent, suggesting that training on tasks requiring coordinated effort of both the upper arm and hand may be a more effective method for improving recovery of real world function. However, most robotic therapies have focused on training the proximal, rather than distal effectors of the upper extremity. This paper describes the effects of robotically-assisted, integrated upper extremity training. Methods Twelve subjects post-stroke were trained for eight days on four upper extremity gaming simulations using adaptive robots during 2-3 hour sessions. Results The subjects demonstrated improved proximal stability, smoothness and efficiency of the movement path. This was in concert with improvement in the distal kinematic measures of finger individuation and improved speed. Importantly, these changes were accompanied by a robust 16-second decrease in overall time in the Wolf Motor Function Test and a 24-second decrease in the Jebsen Test of Hand Function. Conclusions Complex gaming simulations interfaced with adaptive robots requiring integrated control of shoulder, elbow, forearm, wrist and finger movements appear to have a substantial effect on improving hemiparetic hand function. We believe that the magnitude of the changes and the stability of the patient's function prior to training, along with maintenance of several aspects of the gains demonstrated at retention make a compelling argument for this approach to training.</p