Biochar Reduced Nitrous Oxide and Carbon Dioxide Emissions from Soil with Different Water and Temperature Cycles

Interactions among biochar, respiration, nitrification, and soils can result in biochar increasing, decreasing, or not impacting greenhouse gas (GHG) emissions. This experiment determined the impact of water-filled porosity (WFP) and corn (Zea mays L.) stover biochar on CO2 and N2O emissions in May (spring) and August (summer). The May experiment contained two N rates [0 and 224 kg Ca(NO3)2–N ha–1], whereas the August had three N rates [0, 224 kg Ca(NO3)2–N ha–1, and 224 kg (NH4)2SO4–N ha–1]. The average temperatures in the May and Augusts 2014 experiments were 14 and 24°C, respectively. Biochar reduced CO2–C emissions in the high WFP Ca(NO3)2 treatment in the May and August experiments 15.4 and 16.3 kg ha–1, respectively. Associated with the CO2–C decrease was a 15.7% reduction in the soil solution dissolved organic C. In addition, N2O–N and CO2–C emissions were not correlated in the May Ca(NO3)2 ha–1 treatment, whereas in the August experiment, N2O–N and CO2–C emissions were correlated (r2 = 0.98, P \u3c 0.01). In August, biochar increased the apparent nitrification from 16 to 25 kg NH4–N (ha × d)–1 in the low WFP (NH4)2SO4treatment, and it did not influence the nitrification rate in the high WFP (NH4)2SO4 treatment. In general, N2O–N emissions increased with WFP and N rate and were reduced 21.7% by biochar. The findings suggest that multiple mechanisms contributed to N2O emissions and seasonal differences in soil temperature could result in biochar having a mixed impact on GHG emissions

Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA)

Objective: Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain, but rapid absorption into systemic circulation may limit efficacy and produce untoward effects. We compared the pharmacokinetics of IA triamcinolone acetonide (TA) delivered as an extended-release, microsphere-based formulation (FX006) vs a crystalline suspension (TAcs) in knee OA patients. Method: This Phase 2 open-label study sequentially enrolled 81 patients who received a single IA injection of FX006 (5 mL, 32mg delivered dose, N=63) or TAcs (1 mL, 40mg, N=18). Synovial fluid (SF) aspiration was attempted in each patient at baseline and one post-IA-injection visit (FX006: Week1, Week6, Week12, Week16 or Week20; TAcs: Week6). Blood was collected at baseline and multiple post-injection times. TA concentrations (validated LC-MS/MS, geometric means), pharmacokinetics (non-compartmental analysis models), and adverse events (AEs) were assessed. Results: SF TA concentrations following FX006 were quantifiable through Week12 (pg/mL: 231,328.9 at Week1; 3590.0 at Week6; 290.6 at Week12); post-TAcs, only 2 of 8 patients had quantifiable SF TA at Week6 (7.7 pg/mL). Following FX006, plasma TA gradually increased to peak (836.4 pg/mL) over 24 hours and slowly declined to <110 pg/mL over Weeks12-20; following TAcs, plasma TA peaked at 4 hours (9,628.8 pg/mL), decreased to 4,991.1 pg/mL at 24 hours, and was 149.4 pg/mL at Week6, the last post-treatment time point assessed. AEs were similar between groups. Conclusion: In knee OA patients, microsphere-based TA delivery via a single IA injection prolonged SF joint residency, diminished peak plasma levels, and thus reduced systemic TA exposure relative to TAcs

Phosphorylation of Calcineurin at a novel serine-proline rich region orchestrates hyphal growth and virulence in Aspergillus fumigatus.

The fungus Aspergillus fumigatus is a leading infectious killer in immunocompromised patients. Calcineurin, a calmodulin (CaM)-dependent protein phosphatase comprised of calcineurin A (CnaA) and calcineurin B (CnaB) subunits, localizes at the hyphal tips and septa to direct A. fumigatus invasion and virulence. Here we identified a novel serine-proline rich region (SPRR) located between two conserved CnaA domains, the CnaB-binding helix and the CaM-binding domain, that is evolutionarily conserved and unique to filamentous fungi and also completely absent in human calcineurin. Phosphopeptide enrichment and tandem mass spectrometry revealed the phosphorylation of A. fumigatus CnaA in vivo at four clustered serine residues (S406, S408, S410 and S413) in the SPRR. Mutation of the SPRR serine residues to block phosphorylation led to significant hyphal growth and virulence defects, indicating the requirement of calcineurin phosphorylation at the SPRR for its activity and function. Complementation analyses of the A. fumigatus ΔcnaA strain with cnaA homologs from the pathogenic basidiomycete Cryptococcus neoformans, the pathogenic zygomycete Mucor circinelloides, the closely related filamentous fungi Neurospora crassa, and the plant pathogen Magnaporthe grisea, revealed filamentous fungal-specific phosphorylation of CnaA in the SPRR and SPRR homology-dependent restoration of hyphal growth. Surprisingly, circular dichroism studies revealed that, despite proximity to the CaM-binding domain of CnaA, phosphorylation of the SPRR does not alter protein folding following CaM binding. Furthermore, mutational analyses in the catalytic domain, CnaB-binding helix, and the CaM-binding domains revealed that while the conserved PxIxIT substrate binding motif in CnaA is indispensable for septal localization, CaM is required for its function at the hyphal septum but not for septal localization. We defined an evolutionarily conserved novel mode of calcineurin regulation by phosphorylation in filamentous fungi in a region absent in humans. These findings suggest the possibility of harnessing this unique SPRR for innovative antifungal drug design to combat invasive aspergillosis

A comparative study of a Financial Agent based Simulator across learning scenarios

modeling financial time series by using agent based simulatio