Perfusion based microfluidic system for pharmacological profiling of neuronal networks

This work presents the integration of a semi-automated microfluidic platform that utilizes calcium imaging to enable the pharmacological characterization of functionally connected, but environmentally isolated neuronal networks. This approach allows, for the first time, to assess the cause-effect relationship of neuronal communication following drug application, thus allowing the pharmacological characterisation of novel drugs proposed to influence communication between neuronal networks

‘Our voice started off as a whisper and now it is a great big roar’ : The Salford Dementia Associate Panel as a model of involvement in research activities

This paper presents the work of the ‘Salford Dementia Associate Panel’, based at the Salford Institute for Dementia, Salford University (UK). We discuss the roles of the Dementia Associates, in particular around the areas of engagement and research. The panel is made up of people living with dementia, and current and former care partners. It highlights the development of this group over a four-year period and demonstrates over time how the role of a Dementia Associate member has evolved. The panel is involved in research, education and public engagement activities conducted by staff and students within the Institute. The motivations for becoming involved are clearly articulated and demonstrate how the personal backgrounds of individuals have driven the collective involvement and desire to bring about change. The benefits and challenges associated with working as part of a panel are discussed. We conclude by bringing together our experiences as a set of suggestions for others who may wish to create a similar forum to promote the involvement of people living with dementia and former and current care partners

Pasture Yield and Animal Performance from Aeschynomene Americana Cultivars Glenn and Lee

An on farm demonstration site was used to promote and compare the performance of the tropical legumes Glenn American jointvetch and Lee American jointvetch (Aeschynomene americana). Both legumes are widely sown in tropical Australia and are being increasingly sown in South-East Asian pasture projects. Glenn and Lee both grew well and persisted in grass/legume pastures over a 5 year period. Liveweight gain of steers, at a stocking rate of 1.5/ha, slightly favoured the Glenn pasture and gains of 0.49 kg/day for a 595 day period were achieved. Soil seed reserves were much higher under the annual Glenn than for the later flowering perennial Lee. Current recommendations are to sow equal portions of Glenn and Lee in legume/grass pasture mixture

More Aeschynomene Pasture Legumes for the Tropics and Sub-Tropics

Two cultivars of Aeschynomene villosa were released in Queensland in 1995. Cultivars ‘Reid’ (previously CPI 91209) and ‘Kretschmer’ (previously CPI 93621) are both native to Mexico and are the first cultivars of A. villosa to be released as pasture legumes. They will complement the three Aeschynomene cultivars already in use in tropical and sub-tropical northern and eastern Australia, namely cultivars ‘Glenn’ and ‘Lee’ (A. americana) and ‘Bargoo’ (A. falcata). Characteristics of Reid and Kretschmer jointvetch include, early seeding perennials within high seed yields, prostrate to semi-erect growth habit, adaptation to a wide range of soil types in medium rainfall areas, tolerance of temporary waterlogging, palatability of high quality forage, responsive to added phosphorus, and tolerance of light frosts. Commercial seed will be available for sale about October, 1997. Reid and Kretschmer villose jointvetch are widely adapted high quality pasture legumes which will complement current legume cultivars and will broaden the scope for sown pasture development in sub-tropical and tropical northern Australia

A 340/380 nm light emitting diode illuminator for Fura-2 AM ratiometric Ca2+ imaging of live cells with better than 5 nM precision

We report the first demonstration of a fast wavelength-switchable 340/380 nm light emitting diode (LED) illuminator for Fura-2 ratiometric Ca2+ imaging of live cells. The LEDs closely match the excitation peaks of bound and free Fura-2 and enables the precise detection of cytosolic Ca2+ concentrations, which is only limited by the Ca2+ response of Fura-2. Using this illuminator, we have shown that Fura-2 acetoxymethyl ester (AM) concentrations as low as 250 nM can be used to detect induced Ca2+ events in tsA-201 cells and while utilizing the 150 µs switching speeds available, it was possible to image spontaneous Ca2+ transients in hippocampal neurons at a rate of 24.39 Hz that were blunted or absent at typical 0.5 Hz acquisition rates. Overall, the sensitivity and acquisition speeds available using this LED illuminator significantly improves the temporal resolution that can be obtained in comparison to current systems and supports optical imaging of fast Ca2+ events using Fura-2

Normal Cones and Thompson Metric

The aim of this paper is to study the basic properties of the Thompson metric $d_T$ in the general case of a real linear space $X$ ordered by a cone $K$. We show that $d_T$ has monotonicity properties which make it compatible with the linear structure. We also prove several convexity properties of $d_T$ and some results concerning the topology of $d_T$, including a brief study of the $d_T$-convergence of monotone sequences. It is shown most of the results are true without any assumption of an Archimedean-type property for $K$. One considers various completeness properties and one studies the relations between them. Since $d_T$ is defined in the context of a generic ordered linear space, with no need of an underlying topological structure, one expects to express its completeness in terms of properties of the ordering, with respect to the linear structure. This is done in this paper and, to the best of our knowledge, this has not been done yet. The Thompson metric $d_T$ and order-unit (semi)norms $|\cdot|_u$ are strongly related and share important properties, as both are defined in terms of the ordered linear structure. Although $d_T$ and $|\cdot|_u$ are only topological (and not metrical) equivalent on $K_u$, we prove that the completeness is a common feature. One proves the completeness of the Thompson metric on a sequentially complete normal cone in a locally convex space. At the end of the paper, it is shown that, in the case of a Banach space, the normality of the cone is also necessary for the completeness of the Thompson metric.Comment: 36 page

TAp73 contributes to the oxidative stress response by regulating protein synthesis.

TAp73 is a transcription factor that plays key roles in brain development, aging, and cancer. At the cellular level, TAp73 is a critical homeostasis-maintaining factor, particularly following oxidative stress. Although major studies focused on TAp73 transcriptional activities have indicated a contribution of TAp73 to cellular metabolism, the mechanisms underlying its role in redox homeostasis have not been completely elucidated. Here we show that TAp73 contributes to the oxidative stress response by participating in the control of protein synthesis. Regulation of mRNA translation occupies a central position in cellular homeostasis during the stress response, often by reducing global rates of protein synthesis and promoting translation of specific mRNAs. TAp73 depletion results in aberrant ribosomal RNA (rRNA) processing and impaired protein synthesis. In particular, polysomal profiles show that TAp73 promotes the integration of mRNAs that encode rRNA-processing factors in polysomes, supporting their translation. Concurrently, TAp73 depletion causes increased sensitivity to oxidative stress that correlates with reduced ATP levels, hyperactivation of AMPK, and translational defects. TAp73 is important for maintaining active translation of mitochondrial transcripts in response to oxidative stress, thus promoting mitochondrial activity. Our results indicate that TAp73 contributes to redox homeostasis by affecting the translational machinery, facilitating the translation of specific mitochondrial transcripts. This study identifies a mechanism by which TAp73 contributes to the oxidative stress response and describes a completely unexpected role for TAp73 in regulating protein synthesis

A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma.

Dysregulated expression of factors that control protein synthesis is associated with poor prognosis of many cancers, but the underlying mechanisms are not well defined. Analysis of the diffuse large B-cell lymphoma (DLBCL) translatome revealed selective upregulation of mRNAs encoding anti-apoptotic and DNA repair proteins. We show that enhanced synthesis of these proteins in DLBCL is mediated by the relief of repression that is normally imposed by structure in the 5'-untranslated regions of their corresponding mRNAs. This process is driven by signaling through mammalian target of rapamycin, resulting in increased synthesis of eukaryotic initiation factor (eIF) 4B complex (eIF4B), a known activator of the RNA helicase eIF4A. Reducing eIF4B expression alone is sufficient to decrease synthesis of proteins associated with enhanced tumor cell survival, namely DAXX, BCL2 and ERCC5. Importantly, eIF4B-driven expression of these key survival proteins is directly correlated with patient outcome, and eIF4B, DAXX and ERCC5 are identified as novel prognostic markers for poor survival in DLBCL. Our work provides new insights into the mechanisms by which the cancer-promoting translational machinery drives lymphomagenesis