Josefsenyang2007

Viral RNAs are susceptible to co-translational RNA decay pathways mediated by the RNA helicase Upstream frameshift 1 (Upf1). Upf1 is a key component in nonsense-mediated decay (NMD), Staufen1-mediated mRNA decay (SMD), and structure-mediated RNA decay (SRD) pathways, among others. Diverse families of viruses have features that predispose them to Upf1 targeting, but have evolved means to escape decay through the action of cis-acting or trans-acting viral factors. Studies aimed at understanding how viruses are subjected to and circumvent NMD have increased our understanding of NMD target selection of host mRNAs. This review focuses on the knowledge gained from studying NMD in viral systems as well as related Upf1-dependent pathways and how these pathways restrict virus replication.Double strand break (DSB) repair through Homologous Recombination (HR) is essential in maintaining genomic stability of the cell. Mutations in the HR pathway confer an increased risk for breast, ovarian, pancreatic and prostate cancer. PARP inhibitors (PARPi) are compounds that specifically target tumours deficient in HR. Novel PARPi are constantly being developed, but research is still heavily focussed on in vitro data, with mouse xenografts only being used in late stages of development. There is a need for assays that can 1) provide in vivo data, 2) early in the development process of novel PARPi, 3) provide fast results and 4) at an affordable cost. Here we propose a combination of in vivo zebrafish assays to accurately quantify PARP inhibitor efficacy. We showed that PARPi display functional effects in zebrafish, generally correlating with their PARP trapping capacities. Furthermore, we displayed how olaparib mediated radiosensitization is conserved in our zebrafish model. These assays could aid the development of novel PARPi by providing early in vivo data. In addition, using zebrafish allows for high-throughput testing of combination therapies in search of novel treatment strategies.A community of aquatic macrophytes has an important role in reducing nutrient load and organic and inorganic contaminants in storm/runoff water. However, minimal information is available regarding the efficiency of constructed wetlands for cleaning runoff water from urban areas, especially in the tropical and subtropical regions. This study investigated the effectiveness of constructed wetland integrated with aquatic macrophytes for removal of chemical and microbial contaminants in the storm/runoff water from the urban areas. Water samples were monthly collected in the constructed wetland from the inlet of storm/runoff water, middle and outlet of discharge, and analyzed for physical and chemical properties, concentrations of nutrients, metals, and fecal coliform (FC) during the period of November, 2016 to April, 2018 in St. Lucie county, Florida, USA. The dominant plant species in the constructed wetland included cattail (Typha latifolia), waterthyme (Hydrilla verticillata) and water hyacinth (Eichhornia crasove the system efficiency for cleaning storm water from urban areas.Understanding the distribution, net primary productivity (NPP) and environmental constraints of Larix kaempferi is crucial to predict how global climate change will affect its growth and future dynamics. We simulated future changes in the globally suitable distribution patterns and the NPP dynamics under different representative concentration pathways (RCPs) using MaxEnt and Physiological Principles in Predicting Growth (3-PG) models. The results showed that suitable distribution areas for Larix kaempferi were concentrated in Europe and Asia, followed by North America, under current climate conditions. Globally, about 33.75% of the suitable area was in China. Suitable areas decreased and shifted northward in Asia, Europe and China in the RCP scenarios. Larix kaempferi could adapt or move to higher latitudes/altitudes to mitigate the negative impacts of climate change. The NPP of Larix kaempferi in China was 241.85-863.57 g m-2 a-1 simulated by the 3-PG model after local parameterization, which was consistent with the measured NPP. Changes in NPP were predicted in future climates. When the correlations between climate factors and NPP were examined, under the more optimistic scenarios, NPP would increase significantly. The key parameters of the 3-PG model were the optimal temperature for growth, forest age, and the number of days of lost productivity in each frost period. Therefore, climate change has a quantitative and significant impact on the distribution and productivity of L. kaempferi, which was estimated successfully with the two modeling approaches. Our results will contribute to the improved cultivation, environment and management of L. kaempferi and potentially of other deciduous gymnosperms.For prospective investigation of drugs and metabolites in archaeological and contemporary dental calculus, a sensitive, broadly applicable ultra-high-performance liquid chromatography-tandem mass spectrometry method using pneumatically assisted electrospray ionisation (UHPLC-ESI-MS/MS) was developed. The dental calculus was treated with citric acid and the dissolution extracts were cleaned using weak and strong polymeric cation-exchange sorbents. The method was validated on hydroxyapatite for the analysis of 67 drugs and metabolites. Typically, the lower limits of quantification were in the range of 0.01-0.05ng for the sample mass extracted. click here The general applicability of the method was tested using dental calculus material sampled from 10 corpses undergoing forensic autopsy. The calculus material was washed several times before dissolution to remove residual substances originating from saliva, gingival crevicular fluid and blood. The wash extracts and the calculus samples (cleaned calculus material) were analysed using the same instrumental conditions. The dry mass of the calculus samples ranged from 1 to 10mg. The total number of drug detections was 131 in the dental calculus samples and 117 in the whole blood samples. From the analyses of the wash extracts and calculus samples, it was proven that drug residues were trapped in the interior of the calculus material. In 82 of the drug detections, the drug concentrations were higher in the dental calculus than in the blood. Among substances detected in the dental calculus but not in the blood were cocaine, heroin, 6-MAM and THCA-A.