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Frontier soils contain up to 177 Gt of C, which might be subject to release, which is the equivalent of over a century of current United States CO2 emissions. Watersheds serving over 1.8 billion people would be impacted by the cultivation of the climate-driven frontiers. Frontiers intersect 19 global biodiversity hotspots and the habitat of 20% of all global restricted range birds. Sound planning and management of climate-driven agricultural frontiers can therefore help reduce globally significant impacts on people, ecosystems and the climate system.Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P less then 0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.Calmodulin sits at the center of molecular mechanisms underlying learning and memory. Its complex and sometimes opposite influences, mediated via the binding to various proteins, are yet to be fully understood. Calcium/calmodulin-dependent protein kinase II (CaMKII) and calcineurin (CaN) both bind open calmodulin, favoring Long-Term Potentiation (LTP) or Depression (LTD) respectively. Neurogranin binds to the closed conformation of calmodulin and its impact on synaptic plasticity is less clear. We set up a mechanistic computational model based on allosteric principles to simulate calmodulin state transitions and its interactions with calcium ions and the three binding partners mentioned above. We simulated calcium spikes at various frequencies and show that neurogranin regulates synaptic plasticity along three modalities. At low spike frequencies, neurogranin inhibits the onset of LTD by limiting CaN activation. At intermediate frequencies, neurogranin facilitates LTD, but limits LTP by precluding binding of CaMKII with calmodulin. Finally, at high spike frequencies, neurogranin promotes LTP by enhancing CaMKII autophosphorylation. While neurogranin might act as a calmodulin buffer, it does not significantly preclude the calmodulin opening by calcium. On the contrary, neurogranin synchronizes the opening of calmodulin's two lobes and promotes their activation at specific frequencies. Neurogranin suppresses basal CaN activity, thus increasing the chance of CaMKII trans-autophosphorylation at high-frequency calcium spikes. Taken together, our study reveals dynamic regulatory roles played by neurogranin on synaptic plasticity, which provide mechanistic explanations for opposing experimental findings.Molecular diagnosis is an essential step of patient care. PTC-209 An increasing number of Copy Number Variations (CNVs) have been identified that are involved in inherited and somatic diseases. However, there are few existing tools to identify them among amplicon sequencing data generated by Next Generation Sequencing (NGS). We present here a new tool, CovCopCan, that allows the rapid and easy detection of CNVs in inherited diseases, as well as somatic data of patients with cancer, even with a low ratio of cancer cells to healthy cells. This tool could be very useful for molecular geneticists to rapidly identify CNVs in an interactive and user-friendly way.BACKGROUND Codonopsis pilosula is a traditional Chinese medicine that has an anti-aging effect. However, the anti-aging effect of Codonopsis pilosula on the lungs remains largely unknown, and the molecular mechanism also needs to be further studied. Thus, we investigated the protective effect of Codonopsis pilosula on the lungs of aging mice, and explored the underlying molecular mechanism. MATERIAL AND METHODS We established an aging mouse model and then treated the mice with Codonopsis pilosula. Microarray analysis and bioinformatics methods were used to comprehensively analyze the lncRNA-miRNA-mRNA (ceRNA) network. RESULTS Our results showed that we successfully established the aging mouse model. The microarray analysis showed that 138 lncRNAs, 128 mRNAs, and 7 miRNAs were significantly changed after aging, and 282 lncRNAs, 283 mRNAs, and 19 miRNAs were dysregulated after treatment with Codonopsis pilosula. To explore the signaling pathways involved, KEGG pathway analysis was performed. Compared with the ceRNA network in aging mice and after treatment with Codonopsis pilosula, we found that 3 mRNAs (Hif3a, Zbtb16, Plxna2) and 1 lncRNA (NONMMUT063872) were associated with the anti-aging effect of Codonopsis pilosula and they were validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. CONCLUSIONS Our results showed that Codonopsis pilosula has a protective effect on the aging lung, and the ceRNA network plays an important role in the anti-aging effect of Codonopsis pilosula.The objective of this study was to compare the efficacy and safety of endoscopic papillary balloon dilation (EPBD), endoscopic sphincterotomy (ES), and the combination of large balloon dilation and ES (ES + EPLBD) in the treatment of common bile duct stones, with a special focus on postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Individualized search strategies were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomized controlled trials (RCTs) which evaluated at least one of the following outcomes PEP, complete stone removal in the first ERCP, need for mechanical lithotripsy, recurrence of common bile duct stones, bleeding, and cholangitis. Twenty-five RCTs were selected for analysis. Pancreatitis rates were higher for EPBD than for ES (P = 0.003), as were severe pancreatitis rates (P = 0.04). However, in the 10-mm or greater balloon subgroup analysis, this difference was not shown (P = 0.82). Rates of PEP were higher in the subgroup of non-Asian subjects (P = 0.

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