Destabilization of The Ornithine Decarboxylase mRNA Transcript by the RNA-Binding Protein Tristetraprolin

Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. In a normal physiological state, ODC is tightly regulated. However, during neoplastic transformation, ODC expression becomes upregulated. The studies described here show that the ODC mRNA transcript is destabilized by the RNA-binding protein tristetraprolin (TTP). We show that TTP is able to bind to the ODC mRNA transcript in both non-transformed RIE-1 cells and transformed Ras12V cells. Moreover, using mouse embryonic fibroblast cell lines that are devoid of a functional TTP protein, we demonstrate that in the absence of TTP both ODC mRNA stability and ODC enzyme activity increase when compared to wild-type cells. Finally, we show that the ODC 3′ untranslated region contains cis acting destabilizing elements that are affected by, but not solely dependent on, TTP expression. Together, these data support the hypothesis that TTP plays a role in the post-transcriptional regulation of the ODC mRNA transcript

The effect of organic compounds on the growth rate of cloud droplets in marine and forest settings

International audienceOrganic matter represents an important fraction of the fine particle aerosol, yet our knowledge of the roles of organics in the activation of aerosol particles into cloud droplets is poor. A cloud condensation nucleus (CCN) counter is used to examine the relative growth rates of cloud droplets for case studies from field measurements on the North Pacific Ocean and in a coniferous forest. A model of the condensational growth of water droplets, on particles dissolving according to their solubility in water, is used to simulate the initial scattering of the droplets as they grow in the CCN counter. Simulations of the growth rates of fine particles sampled in the marine boundary layer of the North Pacific Ocean indicate that the main influence of the marine organic material on the water uptake rate is from its effect on the size distribution of the sulphate. Simulations of the observations of water uptake on biogenic organic aerosol particles sampled in a coniferous forest indicate an impact of the organic on the water uptake rates, but one that is still smaller than that of pure sulphate. The solubility of the organic becomes an important factor in determining the water uptake as the organic mass increases relative to sulphate. The values of the organic component of the hygroscopicity parameter ? that describes the CCN activity were found to be negligible for the marine particles and 0.02?0.05 for the forest particles

Tumor Suppressor Activity of ODC Antizyme in MEK-driven Skin Tumorigenesis

To test the hypothesis that suppression of ornithine decarboxylase (ODC) activity blocks the promotion of target cells in the outer root sheath of the hair follicle initiated by Raf/MEK/ERK activation, we crossed mice overexpressing an activated MEK mutant in the skin (K14-MEK mice) with two transgenic lines overexpressing antizyme (AZ), which binds to ODC and targets it for degradation. K14-MEK mice develop spontaneous skin tumors without initiation or promotion. These mice on the ICR background were crossed with K5-AZ and K6-AZ mice on both the carcinogenesis-resistant C57BL/6 background and the sensitive DBA/2 background. Expression of AZ driven by either the K5 or K6 promoter along with K14-MEK dramatically delayed tumor incidence and reduced tumor multiplicity on both backgrounds compared with littermates expressing the MEK transgene alone. The effect was most remarkable in the MEK/K6-AZ mice from the ICR/D2 F1 cross, where double transgenic mice averaged less than one tumor per mouse for more than 8 weeks, while K14-MEK mice averaged over 13 tumors per mouse at this age. Putrescine was decreased in MEK/AZ tumors, while spermidine and spermine levels were unaffected, suggesting that the primary role played by AZ in this system is to inhibit putrescine accumulation. MEK/AZ tumors did not show evidence of apoptosis, but there was a 15–20% decrease in S-phase cells and a 40–60% decrease in mitotic cells in MEK/AZ tumors. These results indicate that the principal effect of AZ may be to slow cell growth primarily by increasing G2/M transit time

Ornithine Decarboxylase mRNA is Stabilized in an mTORC1-dependent Manner in Ras-transformed Cells

Upon Ras activation, ODC (ornithine decarboxylase) is markedly induced, and numerous studies suggest that ODC expression is controlled by Ras effector pathways. ODC is therefore a potential target in the treatment and prevention of Ras-driven tumours. In the present study we compared ODC mRNA translation profiles and stability in normal and Ras12V-transformed RIE-1 (rat intestinal epithelial) cells. While translation initiation of ODC increased modestly in Ras12V cells, ODC mRNA was stabilized 8-fold. Treatment with the specific mTORC1 [mTOR (mammalian target of rapamycin) complex 1] inhibitor rapamycin or siRNA (small interfering RNA) knockdown of mTOR destabilized the ODC mRNA, but rapamycin had only a minor effect on ODC translation initiation. Inhibition of mTORC1 also reduced the association of the mRNA-binding protein HuR with the ODC transcript. We have shown previously that HuR binding to the ODC 3′UTR (untranslated region) results in significant stabilization of the ODC mRNA, which contains several AU-rich regions within its 3′UTR that may act as regulatory sequences. Analysis of ODC 3′UTR deletion constructs suggests that cis-acting elements between base 1969 and base 2141 of the ODC mRNA act to stabilize the ODC transcript. These experiments thus define a novel mechanism of ODC synthesis control. Regulation of ODC mRNA decay could be an important means of limiting polyamine accumulation and subsequent tumour development

The management of volunteers – what can human resources do? A review and research agenda

There is an increasing interest from scholars and practitioners in understanding how non-profit organizations can design and implement human resources (HR) practices to enhance desirable volunteer attitudes and behaviors. This paper presents a comprehensive overview of existing studies on the relationship between HR practices and volunteering outcomes. We use the ability-motivation-opportunity model (AMO) as a guiding framework to systematically integrate current knowledge on this topic. We identify gaps in existing research and offer detailed suggestions on how scholars can further enhance knowledge on how HR practices can lead to beneficial outcomes for both volunteers and non-profit organizations

Volunteer role mastery and commitment: Can HRM make a difference?

Although the literature on human resource management (HRM) has provided compelling evidence that certain HRM practices can help employees attain the competence and confidence to carry out their role, less is known about the potential impact of HRM practices on volunteers in the context of non-profit organisations. This study addresses this gap by presenting a model that situates role mastery – operationalised as role clarity and self-efficacy – as its centrepiece. Our model suggests that role mastery leads to commitment to the volunteer organisation and that role mastery can be achieved through training and supportive relationships with paid staff. A dual-mediation analysis of survey data from a humanitarian non-profit organisation in the United Kingdom (n=647) supported our theoretical model. We contribute to volunteering theory and practice by identifying tools that non-profit organisations can employ to maximise the role mastery and commitment of volunteers

Macroborer Presence on Corals Increases with Nutrient Input and Promotes Parrotfish Bioerosion

Bioerosion by reef-dwelling organisms influences net carbonate budgets on reefs worldwide. External bioeroders, such as parrotfish and sea urchins, and internal bioeroders, including sponges and lithophagid bivalves, are major contributors to bioerosion on reefs. Despite their importance, few studies have examined how environmental (e.g., nutrients) or biological drivers (e.g., the actions of other bioeroders) may influence bioeroder dynamics on reefs. For example, internal bioeroders could promote external bioerosion by weakening the coral skeletal matrix. Our study investigated: ( 1) whether nutrient supply influences the dynamics between internal and external bioeroders and ( 2) how the presence of a boring bivalve, Lithophaga spp., influences parrotfish bioerosion on massive Porites corals. We hypothesized that nutrient supply would be positively correlated with Lithophaga densities on massive Porites colonies, and that as bivalve density increased, the frequency and intensity of parrotfish bioerosion would increase. To test these hypotheses, we analyzed six time points over a 10-yr period from a time series of benthic images and nitrogen content of a dominant macroalga from the fringing reefs around Moorea, French Polynesia. We found Lithophaga densities were positively correlated with nitrogen availability. Further, massive Porites that are more infested with Lithophaga had both a higher probability of being bitten by parrotfish and a higher density of bite scars from parrotfishes. Our findings indicate that increasing nutrient availability may strengthen the relationship between internal and external bioeroders, suggesting that colonies at more eutrophic sites may experience higher bioerosion rates

Mechanical tuning of the evaporation rate of liquid on crossed fibers

We investigate experimentally the drying of a small volume of perfectly wetting liquid on two crossed fibers. We characterize the drying dynamics for the three liquid morphologies that are encountered in this geometry: drop, column and a mixed morphology, in which a drop and a column coexist. For each morphology, we rationalize our findings with theoretical models that capture the drying kinetics. We find that the evaporation rate depends significantly on the liquid morphology and that the drying of liquid column is faster than the evaporation of the drop and the mixed morphology for a given liquid volume. Finally, we illustrate that shearing a network of fibers reduces the angle between them, changes the morphology towards the column state, and so enhances the drying rate of a volatile liquid deposited on it