The proper processing, export, localization, translation, and degradation of mRNAs are necessary for regulation of gene expression. These processes are controlled by mRNA-specific regulatory ...proteins, noncoding RNAs, and core machineries common to most mRNAs. These factors bind the mRNA in large complexes known as messenger ribonucleoprotein particles (mRNPs). Herein, we review the components of mRNPs, how they assemble and rearrange, and how mRNP composition differentially affects mRNA biogenesis, function, and degradation. We also describe how properties of the mRNP “interactome” lead to emergent principles affecting the control of gene expression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Stress granules are mRNA-protein assemblies formed from nontranslating mRNAs. Stress granules are important in the stress response and may contribute to some degenerative diseases. Here, we describe ...the stress granule transcriptome of yeast and mammalian cells through RNA-sequencing (RNA-seq) analysis of purified stress granule cores and single-molecule fluorescence in situ hybridization (smFISH) validation. While essentially every mRNA, and some noncoding RNAs (ncRNAs), can be targeted to stress granules, the targeting efficiency varies from <1% to >95%. mRNA accumulation in stress granules correlates with longer coding and UTR regions and poor translatability. Quantifying the RNA-seq analysis by smFISH reveals that only 10% of bulk mRNA molecules accumulate in mammalian stress granules and that only 185 genes have more than 50% of their mRNA molecules in stress granules. These results suggest that stress granules may not represent a specific biological program of messenger ribonucleoprotein (mRNP) assembly, but instead form by condensation of nontranslating mRNPs in proportion to their length and lack of association with ribosomes.
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•Purification of stress granule cores identifies RNAs in stress granules•Only ∼10% of bulk mRNA molecules are present in stress granules•Most mRNAs go to stress granules, but the efficiency varies from <1% to >95%•Poor translation efficiency and longer length correlate with targeting to granules
Transcriptome analysis coupled with single-molecule FISH validation of stress granule cores provides new insight into the mRNAs and ncRNAs that accumulate in stress granules. Ten percent of bulk mRNA molecules accumulate in stress granules, and targeting efficiency correlates with poorer translation efficiency and longer coding and UTR length.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This conceptual paper extends theories of gift giving behavior through identifying and defining the emerging phenomenon of Avenger Philanthropy. This manifests when people make individual monetary ...donations to nonprofit organizations (NPOs) to achieve a collective sense of moral grandstanding, usually underpinned by humor. For the first time, the paper makes sense of this phenomenon theoretically through drawing on a wide range of literature including gift giving, game theory and consumer psychology, and as a result, identifies seven distinctive hallmarks. The paper maps the importance of public expression of personal values, amplified through social media, together with risks for the NPO that benefits from the donations. Emotion underpins the giving behavior, both moral outrage and humor. This investigation contributes to the gift giving literature by identifying, mapping and anchoring current actions that potentially have far reaching consequences for future research and for nonprofit practice.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Responding to a call for research into storytelling within the nonprofit context, the paper contributes to an emerging research conversation about communicating organizational strategy through ...storytelling. The research analyses one hundred stories across 10 leading organizations to identify how they are being deployed and what that tells us about the underpinning strategy. Through bringing story character, classification, and content together for the first time, the paper presents a holistic perspective on the story construct. It identifies that, when viewed as a whole, the stories told by organizations can be a powerful communication tool for reaching external audiences. However, the research also identifies that their ability to convey strategic purpose through storytelling is moderated by storytelling capability. It finds that organizations with stronger storytelling capability use this craft to differentiate themselves more effectively. It concludes with contributing a new conceptual model for understanding organizational storytelling and a roadmap for practitioners to strengthen storytelling capability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Circulating levels of undercarboxylated and bioactive osteocalcin double during aerobic exercise at the time levels of insulin decrease. In contrast, circulating levels of osteocalcin plummet early ...during adulthood in mice, monkeys, and humans of both genders. Exploring these observations revealed that osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, the main nutrients of myofibers. Osteocalcin signaling in myofibers also accounts for most of the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise in part by driving the generation of bioactive osteocalcin. We further show that exogenous osteocalcin is sufficient to enhance the exercise capacity of young mice and to restore to 15-month-old mice the exercise capacity of 3-month-old mice. This study uncovers a bone-to-muscle feedforward endocrine axis that favors adaptation to exercise and can reverse the age-induced decline in exercise capacity.
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•Bone via the hormone osteocalcin improves muscle function during exercise•Circulating osteocalcin levels decrease in aging mice, monkeys, and humans•Osteocalcin promotes muscle uptake and utilization of glucose and fatty acids•Osteocalcin promotes muscle IL-6 secretion during exercise
Mera et al. show that the bone-derived hormone osteocalcin is necessary for optimum exercise capacity and that this hormone decreases with aging in mice, monkeys, and humans of both genders. Osteocalcin promotes muscle uptake and utilization of glucose and lipids during exercise and greatly improves the exercise capacity of old mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
Nonprofit organisations (NPOs) are an increasingly fundamental part of our society. Meeting rising demand requires NPOs to attract enough resources, especially volunteers, to enable service ...delivery. This paper aims to adopt a novel theoretical lens to reframe this marketing challenge to inform practice and extend theory.
Design/methodology/approach
Practice-based exploration of a volunteer-enabled NPO, parkrun, through in-depth interviews and secondary source analysis.
Findings
The research identified that the brand community connects volunteers through three inter-connected levels. The big idea of parkrun, the focal brand, resonated with people through being “on their wavelength”, something they believed in. The local, physical event meant engagement was “on their patch”, anchored in place. Finally, the brand community enables people to volunteer “on their terms”, with fluid roles and flexible levels of commitment.
Research limitations/implications
Not all NPOs have service beneficiaries who are able to volunteer, services with different volunteering roles, or operate through a local physical presence. However, taking a focal brand approach to consider the brand community through which people volunteer for an NPO, the practices that reinforce that community, and how to offer volunteers significantly greater flexibility in both role and commitment presents an opportunity for NPOs to rethink how volunteering works for them in the future.
Practical implications
Clear recommendations for practice include the opportunity to integrate service beneficiary with service delivery enabler (volunteer) to strengthen the implicit social contract, increasing participation to deepen the social identity felt towards the brand, and key practices that reduce barriers to volunteering.
Originality/value
The paper extends volunteering theory from the traditional individual needs approach to a focal brand community perspective. The marketing challenge of attracting volunteer resources to NPOs is understood through rethinking the boundaries between service beneficiaries and service enablers, anchored in social identity theory. It provides clear recommendations for practice through reframing the recruitment challenge.
Global analysis of yeast mRNPs Mitchell, Sarah F; Jain, Saumya; She, Meipei ...
Nature structural & molecular biology,
01/2013, Volume:
20, Issue:
1
Journal Article
Peer reviewed
Open access
Proteins regulate gene expression by controlling mRNA biogenesis, localization, translation and decay. Identifying the composition, diversity and function of mRNA-protein complexes (mRNPs) is ...essential to understanding these processes. In a global survey of Saccharomyces cerevisiae mRNA-binding proteins, we identified 120 proteins that cross-link to mRNA, including 66 new mRNA-binding proteins. These include kinases, RNA-modification enzymes, metabolic enzymes and tRNA- and rRNA-metabolism factors. These proteins show dynamic subcellular localization during stress, including assembly into stress granules and processing bodies (P bodies). Cross-linking and immunoprecipitation (CLIP) analyses of the P-body components Pat1, Lsm1, Dhh1 and Sbp1 identified sites of interaction on specific mRNAs, revealing positional binding preferences and co-assembly preferences. When taken together, this work defines the major yeast mRNP proteins, reveals widespread changes in their subcellular location during stress and begins to define assembly rules for P-body mRNPs.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The importance of dietary composition and feeding patterns in aging remains largely unexplored, but was implicated recently in two prominent nonhuman primate studies. Here, we directly compare in ...mice the two diets used in the primate studies focusing on three paradigms: ad libitum (AL), 30% calorie restriction (CR), and single-meal feeding (MF), which accounts for differences in energy density and caloric intake consumed by the AL mice. MF and CR regimes enhanced longevity regardless of diet composition, which alone had no significant impact within feeding regimens. Like CR animals, MF mice ate quickly, imposing periods of extended daily fasting on themselves that produced significant improvements in morbidity and mortality compared with AL. These health and survival benefits conferred by periods of extended daily fasting, independent of dietary composition, have major implications for human health and clinical applicability.
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•The duration of eating/fasting varies based on diet type and feeding protocol•Meal feeding and CR, unlike AL, show high metabolic flexibility in male mice•Eating patterns rather than diet composition influence longevity regulation•A prolonged daily fasting is associated with delayed onset of liver pathologies
Mitchell et al. show that a long daily period of fasting improves the health and survival of male mice, regardless of caloric intake, diet composition, and body weight.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in genes encoding the DNA repair proteins CS group A or B (CSA or CSB). ...Since dietary interventions can alter neurodegenerative processes, Csbm/m mice were given a high-fat, caloric-restricted, or resveratrol-supplemented diet. High-fat feeding rescued the metabolic, transcriptomic, and behavioral phenotypes of Csbm/m mice. Furthermore, premature aging in CS mice, nematodes, and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet, and β-hydroxybutyrate, PARP inhibition, or NAD+ supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB can displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD+, through the deacetylase SIRT1 and suggests possible interventions for CS.
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•Hyperactivation of PARP1 drives SIRT1 depression in Cockayne syndrome (CS)•A high-fat diet, β-hydroxybutyrate, or NAD+ replenishment rescue phenotypes in CS•PARP inhibition and β-hydroxybutyrate increase SIRT1 activity in CS-cells•CSB displaces PARylated PARP1 from damaged DNA and suppresses its activity
Cockayne syndrome group B (CSB) is associated with hyperactivation of the DNA damage response enzyme PARP1 leading to NAD+ depletion, SIRT1 attenuation, and decreased acetyl-CoA formation. Increasing NAD+ or enhancing acetyl-CoA via ketogenesis rescues the accelerated aging. CSB protein interacts with PARP1 to prevent increasing signaling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Recommended Daily Allowance (RDA) for protein intake in the adult population is widely promoted as 0.8 g · kg−1 · d−1. Aging may increase protein requirements, particularly to maintain muscle ...mass.
We investigated whether controlled protein consumption at the current RDA or twice the RDA (2RDA) affects skeletal muscle mass and physical function in elderly men.
In this parallel-group randomized trial, 29 men aged >70 y mean ± SD body mass index (in kg/m2): 28.3 ± 4.2 were provided with a complete diet containing either 0.8 (RDA) or 1.6 (2RDA) g protein · kg−1 · d−1, aimed to balance energy needs. Before treatment and after 10 wk of intervention, whole-body and appendicular lean mass were measured by using dual-energy X-ray absorptiometry. Knee-extension peak power was measured with dynamometry.
Both groups were found to have been in a moderate negative energy balance (mean ± SD RDA: 209 ± 213 kcal/d; 2RDA 145 ± 214 kcal/d; P= 0.427 for difference between the groups). In comparison with RDA, whole-body lean mass increased in 2RDA (P = 0.001; 1.49 ± 1.30 kg, P < 0.001 compared with −0.55 ± 1.49 kg, P = 0.149). This difference was mostly accounted for by an increase in trunk lean mass found in 2RDA (+1.39 ± 1.09 kg, P < 0.001). Appendicular lean mass also decreased in RDA compared with 2RDA (P = 0.022), driven by a reduction in RDA (−0.64 ± 0.91 kg, P = 0.005 compared with 0.11 ± 0.57 kg, P = 0.592). Adjusting for energy imbalances did not alter these findings. Knee-extension peak power was also differently affected (P = 0.012; 26.6 ± 47.7 W, P = 0.015 in 2RDA compared with −11.7 ± 31.0 W, P = 0.180 in RDA).
Consumption of a diet providing 2RDA for protein compared with the current guidelines was found to have beneficial effects on lean body mass and leg power in elderly men. These effects were not explained by differences in energy balance. This trial was registered at the Australia New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12616000310460.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP