967 research outputs found

    Reaper is regulated by IAP-mediated ubiquitination

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    In most cases, apoptotic cell death culminates in the activation of the caspase family of cysteine proteases, leading to the orderly dismantling and elimination of the cell. The IAPs (inhibitors of apoptosis) comprise a family of proteins that oppose caspases and thus act to raise the apoptotic threshold. Disruption of IAP-mediated caspase inhibition has been shown to be an important activity for pro-apoptotic proteins in Drosophila (Reaper, HID, and Grim) and in mammalian cells (Smac/DIABLO and Omi/HtrA2). In addition, in the case of the fly, these proteins are able to stimulate the ubiquitination and degradation of IAPs by a mechanism involving the ubiquitin ligase activity of the IAP itself. In this report, we show that the Drosophila RHG proteins (Reaper, HID, and Grim) are themselves substrates for IAP-mediated ubiquitination. This ubiquitination of Reaper requires IAP ubiquitin-ligase activity and a stable interaction between Reaper and the IAP. Additionally, degradation of Reaper can be blocked by mutating its potential ubiquitination sites. Most importantly, we also show that regulation of Reaper by ubiquitination is a significant factor in determining its biological activity. These data demonstrate a novel function for IAPs and suggest that IAPs and Reaper-like proteins mutually control each other's abundance

    The Influence of Anhedonic Symptom Severity on dmPFC Connectivity in PTSD

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    This study examined resting state functional connectivity (rsFC) of the dorsal medial prefrontal cortex ( dmPFC ) as a function of anhedonia in individuals with posttraumatic stress disorder (PTSD). Results showed that anhedonia positively correlated with hyperconnectivity between the dmPFC and the left retrosplenial cortex. These findings support that anhedonia is associated with increased rsFC within the default mode network (DMN) for PTSD

    Contaminants in commercial preparations of ‘purified’ small leucine-rich proteoglycans may distort mechanistic studies

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    The authors are grateful to Genodisc (EC’s 7th Framework Programme (FP7, 2007-2013) under grant agreement no. HEALTH-F2-2008-201626) and the Orthopaedic Institute Ltd for funding.This paper reports the perplexing results that came about because of seriously impure commercially available reagents. Commercial reagents and chemicals are routinely ordered by scientists and are expected to have been rigorously assessed for their purity. Unfortunately, we found this assumption to be risky. Extensive work was carried out within our laboratory using commercially-sourced preparations of the small leucine-rich proteoglycans, decorin and biglycan, to investigate their influence on nerve cell growth. Unusual results compelled us to analyse the composition and purity of both preparations of these proteoglycans using both mass spectrometry and Western blotting, with and without various enzymatic deglycosylations. Commercial ‘decorin’ and ‘biglycan’ were found to contain a mixture of proteoglycans including not only both decorin and biglycan but also fibromodulin and aggrecan. The unexpected effects of ‘decorin’ and ‘biglycan’ on nerve cell growth could be explained by these impurities. Decorin and biglycan contain either chondroitin or dermatan sulphate glycosaminoglycan chains whilst fibromodulin only contains keratan sulphate and the large (>2,500 kDa), highly glycosylated aggrecan, contains both keratan and chondroitin sulphate. The different structure, molecular weights and composition of these impurities significantly affected our work and any conclusions that could be made. These findings beg the question as to whether scientists need to verify the purity of each commercially obtained reagent used in their experiments. The implications of these findings are vast, since the effects of these impurities may already have led to inaccurate conclusions and reports in the literature with concomitant loss of researchers’ funds and time.Publisher PDFPeer reviewe

    Trio Concert Dance: Alessandra Ferri, Herman Cornejo, Bruce Levingston. Honors Spring Convocation 2016

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    Legendary dancer Alessandra Ferri, one of the world’s most celebrated dancers, holds the rare title of prima ballerina assoluta. She was recently awarded the coveted Olivier Award for a second time in London. Herman Cornejo, an Argentinian ballet star who, at 16, was the youngest winner of Moscow International Ballet Competition, is a virtuoso dancer in the American Ballet Theatre. Bruce Levingston, who recently performed a sold-out concert at Carnegie Hall, has been hailed by The New Yorker as “a force for new music” and The New York Times for his “mastery of colors and nuance.” Ferri, Cornejo and Levingston will present a night of choreographed works, and Levingston will perform the music of Chopin, Debussy, Glass, Mozart, Rachmaninoff and Satie. Levingston also will be joined by other musicians from Ole Miss to create a musical ambiance that will highlight these illustrious dancers’ magical art. The three performers have performed to critical acclaim throughout the world. One critic wrote of their New York City premiere performance together: “The combination of these three great artists is more than the sum of its parts. The Ferri-Cornejo partnership is as full of rapture and poetry as that legendary pairing of Fonteyn and Nureyev. “For his part, pianist Bruce Levingston was the perfect third to bring in and elevate this into a true concert and dance performance. Levingston’s playing was sublime throughout.” Ferri, Cornejo and Levingston will perform works together that have been created especially for them by such distinguished choreographers as Russell Maliphant and Wayne McGregor. Cornejo also will perform a tango that he choreographed, and Levingston will play a number of solo works from his most recent recording.https://egrove.olemiss.edu/hoco_convo/1005/thumbnail.jp

    The development and optimisation of a primary care-based whole system complex intervention (CARE Plus) for patients with multimorbidity living in areas of high socioeconomic deprivation

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    <B>OBJECTIVES</B> To develop and optimise a primary care-based complex intervention (CARE Plus) to enhance the quality of life of patients with multimorbidity in the deprived areas. <B>METHODS</B> Six co-design discussion groups involving 32 participants were held separately with multimorbid patients from the deprived areas, voluntary organisations, general practitioners and practice nurses working in the deprived areas. This was followed by piloting in two practices and further optimisation based on interviews with 11 general practitioners, 2 practice nurses and 6 participating multimorbid patients. <B>RESULTS</B> Participants endorsed the need for longer consultations, relational continuity and a holistic approach. All felt that training and support of the health care staff was important. Most participants welcomed the idea of additional self-management support, though some practitioners were dubious about whether patients would use it. The pilot study led to changes including a revised care plan, the inclusion of mindfulness-based stress reduction techniques in the support of practitioners and patients, and the stream-lining of the written self-management support material for patients. <B>DISCUSSION</B> We have co-designed and optimised an augmented primary care intervention involving a whole-system approach to enhance quality of life in multimorbid patients living in the deprived areas. CARE Plus will next be tested in a phase 2 cluster randomised controlled trial

    The influence of socioeconomic deprivation on multimorbidity at different ages:a cross-sectional study

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    Multimorbidity occurs at a younger age in individuals in areas of high socioeconomic deprivation but little is known about the 'typology' of multimorbidity in different age groups and its association with socioeconomic status

    Intersyngenic variations in the esterases of bacterized Paramecium aurelia

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    The esterase isozymes were surveyed in bacterized stocks representative of all 14 syngens of Paramecium aurelia by starch gel electrophoresis. The properties of substrate specificity and independent variation of particular isozymes permit the ordering of the differences observed among stocks. Differences can arise from several sources: bacterial variation, intrasyngenic variation, and intersyngenic variation. Bacterial esterases tend to be found in certain zonal areas (see Rowe et al. , 1971) and produce minor stock differences, which are erratic in their distribution. Unlike the situation found in Tetrahymena pyriformis , major intrasyngenic variations are rare in P. aurelia except in syngen 2. This lack of intrasyngenic variation is significant in view of the wide differences in geographic origin and micronuclear chromosome numbers among stocks within a syngen. It suggests that certain esterase genotypes must be under stringent selection within a syngen. The lack of intrasyngenic variation permits assessment of intersyngenic relationships. Syngens differ in a complex way from each other, suggesting that several gene differences may be involved. The syngens can be classified on the basis of their esterases. Syngens which have been shown to be more closely related in terms of cross-mating, breeding systems, and other criteria tend to be more similar in their esterase isozymes. The isozyme technique confirms relationships previously suggested among syngens and offers the promise of eventual assessment of evolutionary distances among syngens. However, establishment of these relationships will be clearer in the absence of bacteria.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44169/1/10528_2004_Article_BF00485641.pd
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