Ageing, drama and creativity: translating research into practice

Ageing, Drama, and Creativity was a pilot six-session interprofessional training course delivered collaboratively by Keele University and the New Vic Theatre, Newcastle-under-Lyme, as part of our Arts and Humanities Research Council (AHRC) funded Ages and Stages follow-on project. The course brought together a critical gerontological approach with arts-based educational practices and was designed to develop practice capabilities and age awareness among a diverse group of professionals working in arts organizations, the voluntary sector, local government, health and social services, and housing. This article describes how the course was developed and how participants were selected, details its aims and objectives, provides an overview of the sessions and a flavor of some of the exercises that were used, and considers findings from the structured evaluation alongside written reflections from participants

Layer dependent neural modulation of a realistic layered-microcircuit model in visual cortex based on bottom-up and top-down signals

The visual attention allocates its resources of information processing to selected sensory inputs for reducing the load of the processing. Here, we carried out the large-scale simulation with the layered-microcircuit model of the visual cortex based on the current knowledge of cortical neurobiology in order to explore the complex interaction between bottom-up visual input and top-down attentional signal. The visual microcircuit model consisted of about 40,000 integrate-and-fire model neurons and represented layers 2/3, 4, 5 and 6 (Tobias C. Potjans, et al., 2009). Two these microcircuits interacted by lateral inhibition through layer 2/3. Top-down attention was applied to layer 2/3 to facilitate the process of visual stimuli. In order to investigate the mechanism of visual processing and attentional effect in the layered-microcircuit model, we simulated a model with a variety of lateral inhibition and compared to physiological results for neural and attentional modulation (Reynolds et al., 1999). Specifically, a model with the lateral inhibition between presynaptic excitatory and postsynaptic inhibitory neurons indicated the layer-dependent modulation due to the presentation of the anti-preferred stimulus, which suppressed the response to the preferred stimulus in output layers such as layers 2/3 and 5. However, attention recovered the response to the preferred stimulus in these layers. These modulations due to the stimuli and attention agreed with the physiology. The general principle of the canonical cortical circuit was the detailed structure of a column, top-down attentional bias to layer 2/3 and the lateral inhibition from presynaptic excitatory to postsynaptic inhibitory neurons through layer 2/3. Our model allowed us to investigate how the bottom-up visual input and the top-down attentional signal may interact with each other in the laminar structure of the column. These results and functions provided important prediction for attention in visual processing

A direct image of the obscuring disk surrounding an active galactic nucleus

Active galactic nuclei (AGN) are generally accepted to be powered by the release of gravitational energy in a compact accretion disk surrounding a massive black hole. Such disks are also necessary to collimate powerful radio jets seen in some AGN. The unifying classification schemes for AGN further propose that differences in their appearance can be attributed to the opacity of the accreting material, which may obstruct our view of the central region of some systems. The popular model for the obscuring medium is a parsec-scale disk of dense molecular gas, although evidence for such disks has been mostly indirect, as their angular size is much smaller than the resolution of conventional telescopes. Here we report the first direct images of a pc-scale disk of ionised gas within the nucleus of NGC 1068, the archetype of obscured AGN. The disk is viewed nearly edge-on, and individual clouds within the ionised disk are opaque to high-energy radiation, consistent with the unifying classification scheme. In projection, the disk and AGN axes align, from which we infer that the ionised gas disk traces the outer regions of the long-sought inner accretion disk.Comment: 14 pages, LaTeX, PSfig, to appear in Nature. also available at http://hethp.mpe-garching.mpg.de/Preprint

Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration

Microglia are the resident innate immune cells in the brain with a major role in orchestrating immune responses. They also provide a frontline of host defense in the central nervous system (CNS) through their active phagocytic capability. Being a professional phagocyte, microglia participate in phagocytic and autophagic clearance of cellular waste and debris as well as toxic protein aggregates, which relies on optimal lysosomal acidification and function. Defective microglial lysosomal acidification leads to impaired phagocytic and autophagic functions which result in the perpetuation of neuroinflammation and progression of neurodegeneration. Reacidification of impaired lysosomes in microglia has been shown to reverse neurodegenerative pathology in Alzheimer's disease. In this review, we summarize key factors and mechanisms contributing to lysosomal acidification impairment and the associated phagocytic and autophagic dysfunction in microglia, and how these defects contribute to neuroinflammation and neurodegeneration. We further discuss techniques to monitor lysosomal pH and therapeutic agents that can reacidify impaired lysosomes in microglia under disease conditions. Finally, we propose future directions to investigate the role of microglial lysosomal acidification in lysosome-mitochondria crosstalk and in neuron-glia interaction for more comprehensive understanding of its broader CNS physiological and pathological implications

A Normalization Model of Attentional Modulation of Single Unit Responses

Although many studies have shown that attention to a stimulus can enhance the responses of individual cortical sensory neurons, little is known about how attention accomplishes this change in response. Here, we propose that attention-based changes in neuronal responses depend on the same response normalization mechanism that adjusts sensory responses whenever multiple stimuli are present. We have implemented a model of attention that assumes that attention works only through this normalization mechanism, and show that it can replicate key effects of attention. The model successfully explains how attention changes the gain of responses to individual stimuli and also why modulation by attention is more robust and not a simple gain change when multiple stimuli are present inside a neuron's receptive field. Additionally, the model accounts well for physiological data that measure separately attentional modulation and sensory normalization of the responses of individual neurons in area MT in visual cortex. The proposal that attention works through a normalization mechanism sheds new light a broad range of observations on how attention alters the representation of sensory information in cerebral cortex

IL7 receptor signalling in T cells: a mathematical modelling perspective

Interleukin‐7 (IL7) plays a nonredundant role in T cell survival and homeostasis, which is illustrated in the severe T cell lymphopenia of IL7‐deficient mice, or demonstrated in animals or humans that lack expression of either the IL7Rα or γ c chain, the two subunits that constitute the functional IL7 receptor. Remarkably, IL7 is not expressed by T cells themselves, but produced in limited amounts by radio‐resistant stromal cells. Thus, T cells need to constantly compete for IL7 to survive. How T cells maintain homeostasis and further maximize the size of the peripheral T cell pool in face of such competition are important questions that have fascinated both immunologists and mathematicians for a long time. Exceptionally, IL7 downregulates expression of its own receptor, so that IL7‐signaled T cells do not consume extracellular IL7, and thus, the remaining extracellular IL7 can be shared among unsignaled T cells. Such an altruistic behavior of the IL7Rα chain is quite unique among members of the γ c cytokine receptor family. However, the consequences of this altruistic signaling behavior at the molecular, single cell and population levels are less well understood and require further investigation. In this regard, mathematical modeling of how a limited resource can be shared, while maintaining the clonal diversity of the T cell pool, can help decipher the molecular or cellular mechanisms that regulate T cell homeostasis. Thus, the current review aims to provide a mathematical modeling perspective of IL7‐dependent T cell homeostasis at the molecular, cellular and population levels, in the context of recent advances in our understanding of the IL7 biology

The unresolved safety concerns of bovine thrombin

A recent review has suggested that bovine thrombin is not associated with an increased risk of bleeding in surgical populations. In spite of extremely limited evidence available, many valuable resources (e.g. safety surveillance and post-marketing programs, case reports) were excluded in reaching this conclusion. While waiting for the adequately powered, controlled clinical trials to address the effects of bovine thrombin on bleeding and thrombotic events, the potential risk cannot be simply ignored. Rather, continued vigilance in the post-surgical setting for bleeding events that may be associated with the development of acquired coagulation factor inhibitors following bovine thrombin administration is warranted