1,044 research outputs found

    Hijacking ZIP codes: posttanscriptional regulation of CCN2 by nucleophosmin

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    CCN2 (connective tissue growth factor [CTGF]/hypertrophic chondrocyte-specific gene product 24 [Hcs24]) is regulated at the transcriptional and posttranscriptional level. For example, an element in the its 3′ untranslated region (3′-UTR) of the CCN2 mRNA controls message stability in chondrocytes. In a recent study, Mukudai et al. (Mol Cell Biol 28:6134-6147, 2008) purified and identified a trans-factor protein binding to the minimal repressive cis element in the 3′-UTR of ccn2 mRNA and identify this protein as the multifunctional nucleolar phosphoprotein nucleophosmin (NPM) This commentary summarizes these observations

    Using virtual experiences of older age: exploring pedagogical and psychological experiences of students

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    Fostering intergenerational empathy is vital for creating an age-friendly society and an important aim for Sport and Exercise Science (SES) degree programmes given that graduates are increasingly entering the healthcare workforce supporting older adults (British Association of Sport and Exercise Sciences; BASES, 2018). Interventions to challenge negative stereotypes of ageing, generate empathy for older adults, and help University students gain experience of ‘being’ an older person have demonstrated mixed success (e.g., Prior & Sargent-Cox, 2014). Recent studies indicate the promise of virtual reality in this context but do not present conclusive evidence for this effect (e.g., Banakou, Kishore, & Slater, 2018). Thus this study explored SES students’ responses to virtual experiences of being an older person in a workshop. Participants completed the “Become Victor” module of the FrailtySIM© application, based on real life experience of an older person in their home, and, a University-developed immersive experience of being an older person in a social situation. Fifty-two students completed questionnaires about their experience of “Become Victor” and 15 students were interviewed (12 in 2 focus groups, 3 individually) about their experiences of both simulations. Data indicated that “Become Victor” offered students insight into being an older person that was “eye-opening” and realistic but frustrating and stressful. The social situation effectively simulated the isolation felt by some older people to an extent, but needed to be more interactive. Students felt that the simulations were important for contextualising previously delivered lecture material on older adults. Future workshop iterations will integrate lecture and virtual experiences using opportunities for student reflection on their experiences

    Dynamic moisture loss explored through quantitative super-resolution microscopy, spatial micro-viscosity and macroscopic analyses in acid milk gels

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    Molecular interactions and dynamic changes at a range of length scales affect the structuring of food materials, as such it is essential to explore structure at a range of different length scales. Herein, four acid milk gel samples are produced from either fresh or reconstituted skim milk that either had no heat treatment or had undergone heat treatment at 85 °C for 10 min. Milk acid gels demonstrate complex structure on a range of length scales of interest in colloidal materials and exhibit different macroscopic and water binding properties. A method is presented to measure the dynamic moisture loss in these samples, without applying external force. Super-resolution microscopy images are quantitatively analysed to describe the gel microstructure with precise features. Fluorescent Lifetime Imaging Microscopy is used to spatially resolve differences in molecular confinement across the sample's microstructure, which is quantified for each sample. Moisture loss and microstructural analyses are correlated to bulk and macroscopic properties determined through rheological and texture analysis, pH and conductivity measurements. More severe thermal and processing treatments leads to a reduction in moisture loss over time. Differences in moisture loss and mechanical properties relate to different thermal processing histories, but are not fully explained by levels of denatured whey proteins, and appear related to changes in mineral balance. The methods presented provide a comprehensive and complementary overview of material properties across relevant length scales and relevant sample conditions

    Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

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    Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention
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