The Adenylate-Uridylate-Rich element RNA binding protein ZFP36L1 suppresses replication stress-induced genomic instability

The RNA binding protein (RBP) ZFP36L1, which binds to adenylate/uridylate (AU)-rich elements (AREs) (AU-RBP) in the 3’ untranslated region of many messenger RNAs, has been extensively characterised for its role in post-transcriptional control of gene expression and is reported as a newly identified cancer driver gene. Replication stress (RS) threatens DNA replication fidelity and stability of the genome. Recently, a small number of AU-RBPs have emerged as key figures in the maintenance of genome integrity through mechanisms that govern the replication stress response and DNA repair. Herein, we report that treatment with low doses of aphidicolin results in hallmarks of RS-associated genomic instability in a cellular model depleted of ZFP36L1 using CRISPR/Cas9. We find that loss of ZFP36L1 results in defects in mitosis leading to chromosome segregation errors and genomic instability. Remarkably, we also identify loss of ZFP36L1 increases the prevalence of FANCD2-associated anaphase ultra-fine bridges indicating chromatid non-disjunction at intrinsically labile common fragile site loci. Furthermore, we detected an increase in RPA and γH2AX foci in S/G2 cells indicative of replication stress-induced DNA damage potentially indicating chronic replication fork stalling and double-strand break formation as demonstrated by increased γH2AX foci colocalising with 53BP1. Surprisingly, chromatin enrichment of U-2OS, HCT116 and Hela cells demonstrated that ZFP36L1 is physically bound to chromatin fractions. Here we also demonstrated the specificity of CRISPR-Cas9 mediated ablation of ZFP36L1 through the inducible expression of ZFP36L1 that demonstrated suppression of 53BP1 nuclear bodies (NBs) and micronuclei formation. Importantly, we demonstrate, by overexpression of a catalytically inactive mutant of human RNase H1 tagged with GFP that loss of ZFP36L1 induces R-loop formation. We also implicate unscheduled R-loop formation as a potential cause for replication stress associated genomic instability through the expression of wild-type RNase H1 which was able to limit the occurrence of 53BP1 NBs in G1 phase cells and RPA in S/G2 phase cells. Finally, we highlight potential ZFP36L1 interactions through mass spectrometry that uncover proteins involved in the maintenance of genome integrity and R-loop resolution. Taken together, our work highlights an important, yet previously unidentified role, for ZFP36L1 in preserving genomic stability including limiting the formation of R-loops in response to replication stress

Success factors in the development of farm vacation tourism

Farm vacation tourism allows many families to fully use their domestic resources; furthermore it generates social benefits for the surrounding community. We have conducted a study to examine the success factors of this type of tourism. The results clearly demonstrate that one of the key components relies on the entrepreneurial skills of the farmer

Success Factors in the Development of Farm Vacation Tourism

Community/Rural/Urban Development,

Tradizione e tecnologia online a confronto. Il passaparola elettronico: perchè l'imprenditore agrituristico dovrebbe tenerne conto

Il passaparola elettronico può aiutare gli operatori agrituristici a relazionarsi in maniera più efficace con il consumatore. Il presente lavoro analizza, attraverso un esperimento, il grado di fiducia che hanno gli utenti nei riguardi delle recensioni digitali e offre degli spunti di riflessione per la commercializzazione dell’agriturismo in Internet

The Impact of Online Reviews on the Choice of Holiday Accommodations

The Impact of Online Reviews on the Choice of HolidayAccommodationsKatia Laura Sidali,Holger Schulze, andAchim SpillerUniversity of G\uf6ttingen{Katia-Laura.Sidali, H.Schulze, A.Spiller}@agr.uni-goettingen.deAbstractIn order to reduce information asymmetries in the tourist industry, consumers refer to multipleinformation sources. Among these, e-reviews are supposed to better reflect quality ofinformation because they are based on consumers\u2019 past experiences. The first purpose of thisstudy is therefore to test within an experimental design whether e-reviews have a predominantor a complementary role on consumer behaviour in comparison with other sources ofinformation (hotel rating system, travel guides and recommendations of travel agents). Asexpected, e-reviews are the most referential information source. We further use a causal modelin order to detect the determinants of trust in e-reviews, and we can show that perceivedexpertness of e-reviews, credibility of the e-platform and brand familiarity explain more than60% of trust in e-reviews. The final part of the analysis is dedicated to our third researchpurpose which is the measurement of the impact of trust in e-reviews on choice ofaccommodations. A significant and positive influence can be demonstrated. Hence, scientificand managerial implications are discussed

A Technology Acceptance Model of common bean growers' intention to adopt Integrated Production in the Brazilian Central Region.

The Brazilian government encouraged the Integrated Production (IP) farming system adoption to mitigate the negative environmental impacts of intensive bean production in irrigated areas of the Brazilian savanna. By ensuring food-safety and the use of sustainable agricultural practices, IP may strengthen national agriculture competitiveness. Regardless of the government efforts to promote IP in the main agricultural regions and among the largest food growers, only few slowly adopted it. Therefore, studying the process of technology adoption is important to identify possible problems that could affect adoption and diffusion of this farming system. We applied a Technology Acceptance Model (TAM) to explain the adoption and use of IP by the common beans growers from one of the most important bean production regions in Brazil. Ninety-three interviews were administered to different actors involved in beans production. A Structural Equation Model (SEM) following a confirmatory factor analysis (CFA) was used to identify the relationship between factors. The findings suggest that respondents have positive perceptions toward adopting IP. Perceived usefulness has a positive impact on attitude, and attitudes affect behavioral intention. However, the proposed model only partially explains IP adoption intentions

Identification of Two-shaft Gas Turbine Variables Using a Decoupled Multi-model Approach With Genetic Algorithm

In industrial practice, the representation of the dynamics of nonlinear systems by models linking their different operating variables requires an identification procedure to characterize their behavior from experimental data. This article proposes the identification of the variables of a two-shafts gas turbine based on a decoupled multi-model approach with genetic algorithm. Hence the multi-model is determined in the form of a weighted combination of the decoupled linear local state space sub-models, with optimization of an objective cost function in different modes of operation of this machine. This makes it possible to have robust and reliable models using input / output data collected on the examined system, limiting the influence of errors and identification noises

Agritourism: A Hedonic Approach of Quality Tourism Indicators in South Tyrol

This paper examines the prices of agritourism accommodation that include food services (i.e., the option to have breakfast) and related farm attributes. We analyze what tourists are willing to pay per night for a designated farm holiday stay in South Tyrol offered through the \u201cRed Rooster\u201d brand (n = 367). We first identify factors that may influence tourist decisions to book a holiday at a farm, which include the number of flowers (i.e., the red rooster quality-rating scheme), the type of accommodation, the distance to various leisure activities, and externalities related to agricultural practices. Second, the paper develops two hedonic models to estimate implicit prices for farm holiday accommodation rates. Specifically, the dependent variables are the prices paid by guests during the summer peak and low seasons. Independent variables are various accommodation attributes, the quality of food service, and the range of possible activities in the area surrounding the farm. The results of the study show that the red rooster quality-rating scheme (i.e., the number of flowers) and the quality of food services are highly significant and have a positive impact on guest willingness to pay. Farm types, such as fruit-growing and livestock operations, have a significant but negative effect on accommodation rates at least during the peak season, whilst wine production and organic farming display a positive influence on the accommodation rates during the low season. Implications for practitioners and policy-makers are discussed