Ion channel diversity, channel expression and function in the choroid plexuses

Knowledge of the diversity of ion channel form and function has increased enormously over the last 25 years. The initial impetus in channel discovery came with the introduction of the patch clamp method in 1981. Functional data from patch clamp experiments have subsequently been augmented by molecular studies which have determined channel structures. Thus the introduction of patch clamp methods to study ion channel expression in the choroid plexus represents an important step forward in our knowledge understanding of the process of CSF secretion

Automatic mental processes, automatic actions and behaviours in game transfer phenomena: an empirical self-report study using online forum data

Previous studies have demonstrated that the playing of videogames can have both intended and unintended effects. The purpose of this study was to investigate the influence of videogames on players’ mental processes and behaviours in day-to-day settings. A total of 1,023 self-reports from 762 gamers collected from online videogame forums were classified, quantified, described and explained. The data include automatic thoughts, sensations and impulses, automatic mental replays of the game in real life, and voluntary/involuntary behaviours with videogame content. Many gamers reported that they had responded – at least sometimes – to real life stimuli as if they were still playing videogames. This included overreactions, avoidances, and involuntary movements of limbs. These experiences lasted relatively short periods of time but in a minority of players were recurrent. The gamers' experiences appeared to be enhanced by virtual embodiment, repetitive manipulation of game controls, and their gaming habits. However, similar phenomena may also occur when doing other non-gaming activities. The implications of these game transfer experiences are discussed

ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors

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Control of position and movement is simplified by combined muscle spindle and Golgi tendon organ feedback

Whereas muscle spindles play a prominent role in current theories of human motor control, Golgi tendon organs (GTO) and their associated tendons are often neglected. This is surprising since there is ample evidence that both tendons and GTOs contribute importantly to neuromusculoskeletal dynamics. Using detailed musculoskeletal models, we provide evidence that simple feedback using muscle spindles alone results in very poor control of joint position and movement since muscle spindles cannot sense changes in tendon length that occur with changes in muscle force. We propose that a combination of spindle and GTO afferents can provide an estimate of muscle-tendon complex length, which can be effectively used for low-level feedback during both postural and movement tasks. The feasibility of the proposed scheme was tested using detailed musculoskeletal models of the human arm. Responses to transient and static perturbations were simulated using a 1-degree-of-freedom (DOF) model of the arm and showed that the combined feedback enabled the system to respond faster, reach steady state faster, and achieve smaller static position errors. Finally, we incorporated the proposed scheme in an optimally controlled 2-DOF model of the arm for fast point-to-point shoulder and elbow movements. Simulations showed that the proposed feedback could be easily incorporated in the optimal control framework without complicating the computation of the optimal control solution, yet greatly enhancing the system's response to perturbations. The theoretical analyses in this study might furthermore provide insight about the strong physiological couplings found between muscle spindle and GTO afferents in the human nervous system. © 2013 the American Physiological Society

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD

Social capital theory: a cross-cutting analytic for teacher/therapist work in integrating children's services?

Reviewing relevant policy, this article argues that the current 'integration interlude' is concerned with reformation of work relations to create new forms of 'social capital'. The conceptual framework of social capital has been used by government policy-makers and academic researchers to examine different types, configurations and qualities of relationships, including professional relations, and how these may function as resources. Focusing on the co-work of teachers and speech and language therapists, this analysis introduces social capital as a means of understanding the impact of integrating children's services on professional practitioner groups and across agencies. Social capital theory is compared to alternative theoretical perspectives such as systems and discourse theories and explored as an analytic offering a multi-level typology and conceptual framework for understanding the effects of policy and governance on interprofessional working and relationships. A previous application of social capital theory in a literature review is introduced and analysed, and instances of the additionality provided by a social capital analysis is offered. The article concludes that amongst the effects of current policy to re-design children's services are the reconstruction of professionals' knowledge/s and practices, so it is essential that such policy processes that have complex and far-reaching effects are transparent and coherent. It is also important that new social capital relations in children's services are produced by groups representative of all involved, importantly including those practitioner groups charged in policy to work differently together in future integrated services

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Stimulus-dependent maximum entropy models of neural population codes

Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. To be able to infer a model for this distribution from large-scale neural recordings, we introduce a stimulus-dependent maximum entropy (SDME) model---a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. The model is able to capture the single-cell response properties as well as the correlations in neural spiking due to shared stimulus and due to effective neuron-to-neuron connections. Here we show that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. As a result, the SDME model gives a more accurate account of single cell responses and in particular outperforms uncoupled models in reproducing the distributions of codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like surprise and information transmission in a neural population.Comment: 11 pages, 7 figure

Synaptic Responses Evoked by Tactile Stimuli in Purkinje Cells in Mouse Cerebellar Cortex Crus II In Vivo

Sensory stimuli evoke responses in cerebellar Purkinje cells (PCs) via the mossy fiber-granule cell pathway. However, the properties of synaptic responses evoked by tactile stimulation in cerebellar PCs are unknown. The present study investigated the synaptic responses of PCs in response to an air-puff stimulation on the ipsilateral whisker pad in urethane-anesthetized mice.Thirty-three PCs were recorded from 48 urethane-anesthetized adult (6-8-week-old) HA/ICR mice by somatic or dendritic patch-clamp recording and pharmacological methods. Tactile stimulation to the ipsilateral whisker pad was delivered by an air-puff through a 12-gauge stainless steel tube connected with a pressurized injection system. Under current-clamp conditions (I = 0), the air-puff stimulation evoked strong inhibitory postsynaptic potentials (IPSPs) in the somata of PCs. Application of SR95531, a specific GABA(A) receptor antagonist, blocked IPSPs and revealed stimulation-evoked simple spike firing. Under voltage-clamp conditions, tactile stimulation evoked a sequence of transient inward currents followed by strong outward currents in the somata and dendrites in PCs. Application of SR95531 blocked outward currents and revealed excitatory postsynaptic currents (EPSCs) in somata and a temporal summation of parallel fiber EPSCs in PC dendrites. We also demonstrated that PCs respond to both the onset and offset of the air-puff stimulation.These findings indicated that tactile stimulation induced asynchronous parallel fiber excitatory inputs onto the dendrites of PCs, and failed to evoke strong EPSCs and spike firing in PCs, but induced the rapid activation of strong GABA(A) receptor-mediated inhibitory postsynaptic currents in the somata and dendrites of PCs in the cerebellar cortex Crus II in urethane-anesthetized mice

CO2PipeHaz: Quantitative hazard assessment for next generation CO2 pipelines

Without a clear understanding of the hazards associated with the failure of CO2 pipelines, carbon capture and storage (CCS) cannot be considered as a viable proposition for tackling the effects of global warming. Given that CO2 is an asphyxiant at high concentrations, the development of reliable validated pipeline outflow and dispersion models are central to addressing this challenge. This information is pivotal to quantifying all the hazard consequences associated with the failure of CO2 transportation pipelines, which forms the basis for emergency response planning and determining minimum safe distances to populated areas. This paper presents an overview of the main findings of the recently completed CO2PipeHaz project [1] which focussed on the hazard assessment of CO2 pipelines to be employed as an integral part of CCS. Funded by the European Commission FP7 Energy programme, the project's main objective was to address this fundamentally important issue