1,268 research outputs found

    Fluorescence-based proteasome activity profiling

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    With the proteasome emerging as a therapeutic target for cancer treatment, accurate tools for monitoring proteasome (inhibitor) activity are in demand. In this chapter, we describe the synthesis and use of a fluorescent proteasome activity probe that allows for accurate profiling of proteasomal activity in cell lysates, intact cells, and murine and human patient-derived material, with high sensitivity using SDS-PAGE. The probe allows for direct scanning of the gel for fluorescent emission of the distinct proteasomal subunits and circumvents the use of Western blot analysis. Due to its suitable biochemical and biophysical properties, the fluorescent probe can also be used for confocal laser scanning microscopy and flow cytometry-based experiments

    Cellular xenotransplantation of animal cells into people: benefits and risk

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    The main benefit of xenotransplantation is its potential to overcome the worldwide organ shortage experienced in allotransplantation. Allogeneic transplantation is the only successful therapy for several life-threatening diseases, with cell, tissue or organ donation only partially meeting the demand and many patients dying while waiting for treatment. With supply falling short of demand, it is foreseen that the use of porcine material may at some stage overcome the existing gap between organ availability and clinical need. Recently, pig islet cells have been utilised in clinical trials, with safety being demonstrated. Indeed, pig-derived cells present several advantages: i) porcine cells have a stable function and differentiation pattern and are not tumorigenic; ii) pig cells have been shown to meet the physiological needs in large animal models; iii) the source of pig cells can be scaled up to meet demands in a highly standardised manner, and with respect to animal welfare regulations; iv) ‘designated-pathogen-free’ (DPF) pig lines can be produced, which could result in a higher safety profile than allotransplantation itself; v) the risk of zoonosis, which was raised years ago as the major hurdle, has been recently circumvented and is actually viewed as a controlled risk; and vi) immune risks are being circumvented via the use of genetically modified donor animals and encapsulation of porcine cells, particularly for the treatment of diabetes. Overall, the benefit appears to outweigh potential risks with respect to cellular xenotransplantation and this is discussed further in this review

    Incorporating measurement error in n=1 psychological autoregressive modeling

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    Measurement error is omnipresent in psychological data. However, the vast majority of applications of autoregressive time series analyses in psychology do not take measurement error into account. Disregarding measurement error when it is present in the data results in a bias of the autoregressive parameters. We discuss two models that take measurement error into account: An autoregressive model with a white noise term (AR+WN), and an autoregressive moving average (ARMA) model. In a simulation study we compare the parameter recovery performance of these models, and compare this performance for both a Bayesian and frequentist approach. We find that overall, the AR+WN model performs better. Furthermore, we find that for realistic (i.e., small) sample sizes, psychological research would benefit from a Bayesian approach in fitting these models. Finally, we illustrate the effect of disregarding measurement error in an AR(1) model by means of an empirical application on mood data in women. We find that, depending on the person, approximately 30-50% of the total variance was due to measurement error, and that disregarding this measurement error results in a substantial underestimation of the autoregressive parameters.</p

    Toponyms for centers of endemism in Madagascar

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    A biogeographical model was proposed in 2006 to explain the centers of endemism and the importance of riparian forest of some watersheds as refuges or dispersal corridors during paleoclimatic oscillations. Here, we consider these geographical features highlighting their biological and socio-cultural importance. We explain the etymology or eponymy of the major rivers of the retreat - dispersal watersheds, i.e., the drainage basins of Bemarivo, Antainambalana, Mangoro, Manampatrana, Mananara South, Mandrare, Onilahy, Mangoky, Tsiribihina, Betsiboka, Maevarano, Sambirano, and Mahavavy North. We propose a toponymy for each of the 15 centers of endemism and highlight their peculiarities. We named the centers of endemism of Vohimarina, Masoala, Analanjirofo, Tanala, Manombo, Anosy, Ranopiso, Karimbola, Mikea, Menabe, Melaky, Sofia, Ampasindava, Ankify, and Ankarana. We illustrate each center of endemism with a flagship species and report on its natural and cultural histories, and conservation.R&#201;SUM&#201;Un mod&#232;le biog&#233;ographique a &#233;t&#233; propos&#233; en 2006 pour expliquer les centres d&#8217;end&#233;misme de la biodiversit&#233; et l&#8217;importance des ripisylves de certains bassins versants en tant que refuges ou couloirs de dispersion au cours des oscillations pal&#233;oclimatiques. Ici, nous consid&#233;rons ces dispositifs g&#233;ographiques en soulignant leur importance biologique et socio-culturelle. Dans un premier temps, nous expliquons la toponymie ou l&#8217;&#233;ponymie des grands fleuves des bassins refuges et de dispersion, &#224; savoir les bassins de la Bemarivo, de l&#8217;Antainambalana, du Mangoro, de la Manampatrana, de la Mananara du Sud, du Mandrare, de l&#8217;Onilahy, du Mangoky, de la Tsiribihina, de la Betsiboka, de la Maevarano, du Sambirano et de la Mahavavy du Nord. Puis nous proposons une toponymie pour chacun des 17 centres et sous-centres d&#8217;end&#233;misme en justifiant leurs particularit&#233;s. Nous retenons ainsi les centres d&#8217;end&#233;misme de Vohimarina, de l&#8217;Atsinanana (dont Masoala et Analanjirofo), Tanala, de Manombo, de l&#8217;Anosy, d&#8217;Ala maika (dont Ranopiso, Karimbola et Mikea), du Menabe, du Melaky, de la Sofia, d&#8217;Ampasindava, d&#8217;Ankify et de l&#8217;Ankarana. Nous illustrons chacun des centres d&#8217;end&#233;misme avec une esp&#232;ce symbolique et rapportons des aspects de son histoire naturelle et culturelle ainsi que de sa conservation

    Editors' introduction to the special issue “Privilege, vulnerability and care: Interspecies dynamics in rural landscapes”

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    Animals are central actors within rural societies but remain largely invisible within both our empirical and theoretical analyses. Approximately 20 years ago in the pages of this journal, Tovey (2003) pointed to the significance of animals in effectively defining rurality: They are central to the rural economy and society and foster a sense among rural residents that they are organically embedded in an interspecies world. Thus, our shared relations with animals are key to understanding rural social relations and their underlying inequalities and hierarchies. Tovey suggested that it was therefore necessary and appropriate that rural sociology should develop its own approach to including animals in theorising rural society. We believe that such an approach is yet to emerge. The aim of this special issue is to outline what such an approach might look like and to present a diverse range of articles to get it underway. In what follows, then, as editors and contributors, we collectively explore the role and significance of human–animal relations in shaping rural society via a particular focus on relations of privilege, vulnerability and care
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