Kinetic analysis of IgG antibodies to beta-amyloid oligomers with surface plasmon resonance

Surface plasmon resonance was used to investigate the kinetics, affinity, and specificity of binding between anti-Aβ (beta-amyloid) IgG antibodies and oligomeric Aβ. Two factors were needed to accurately characterize the IgG binding kinetics. First, a bivalent model was necessary to properly fit the kinetic association and dissociation sensograms. Second, a high concentration of IgG was necessary to overcome a significant mass transport limitation that existed regardless of oligomer density on the sensor surface. Using high IgG concentrations and bivalent fits, consistent kinetic parameters were found at varying sensor surface ligand densities. A comparison of binding specificity, affinity, and kinetic flux between monoclonal and natural human anti-Aβ IgG antibodies revealed the following findings. First, monoclonal antibodies 6E10 and 4G8 single-site binding affinity is similar between Aβ oligomers and monomers. Second, natural human anti-Aβ IgG binding readily binds Aβ oligomers but does not bind monomers. Third, natural human anti-Aβ IgG binds Aβ oligomers with a higher affinity and kinetic flux than 6E10 and 4G8. Both the current analytical methodology and antibody binding profiles are important for advances in antibody drug development and kinetic biomarker applications for Alzheimer’s disease.     

Highly sensitive and selective uric acid biosensor based on a three-dimensional graphene foam/indium tin oxide glass electrode

A three-dimensional (3D) continuous and interconnected network graphene foam (GF) was synthesized by chemical vapor deposition using nickel foam as a template. The morphologies of the GF were observed by scanning electron microscopy. X-ray diffraction and Raman spectroscopy were used to investigate the structure of GF. The graphene with few layers and defect free was closely coated on the backbone of the 3D nickel foam. After etching nickel, the GF was transferred onto indium tin oxide (ITO) glass, which acted as an electrode to detect uric acid using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The GF/ITO electrode showed a high sensitivity for the detection of uric acid: approximately 9.44 mA mM⁻¹ in the range of 25 nM–0.1 μM and 1.85 mA mM⁻¹ in the range of 0.1–60 μM. The limit of detection of GF/ITO electrode for uric acid is 3 nM. The GF/ITO electrode also showed a high selectivity for the detection of uric acid in the presence of ascorbic acid. This electrode will have a wide range of potential application prospects in electrochemical detection.     

Effect of azoxystrobin and kresoxim‐methyl on rice blast and rice grain yield in China

Sensitivity to azoxystrobin and kresoxim‐methyl of 80 single‐spore isolates of Magnaporthe oryzae was determined. The EC₅₀ values for azoxystrobin and kresoxim‐methyl in inhibiting mycelial growth of the 80 M. oryzae isolates were 0.006–0.056 and 0.024–0.287 µg mL^?1, respectively. The EC₅₀ values for azoxystrobin and kresoxim‐methyl in inhibiting conidial germination of the M. oryzae populations were 0.004–0.051 and 0.012–0.105 µg mL^?1, respectively. There was significant difference in sensitivity to azoxystrobin or kresoxim‐methyl between the tested isolates representing differential sensitivity to carbendazim (MBC) and kitazin P (IBP); however, there was no correlation between this difference in sensitivity to azoxystrobin or kresoxim‐methyl and sensitivity to MBC or IBP, indicating that there was no cross‐resistance between azoxystrobin or kresoxim‐methyl and MBC or IBP. In the protective and curative experiments, kresoxim‐methyl exhibited higher protective and curative activity than azoxystrobin when applied at 150 and 250 µg mL^?1 accordingly, while azoxystrobin exhibited stronger inhibitory activity against M. oryzae isolates than that of kresoxim‐methyl in the in vitro test. The results of field experiments also suggested that both azoxystrobin and kresoxim‐methyl at 187.5 g.a.i. ha^?1 gave over 73% control efficacy in both sites, exhibiting excellent activity against rice blast. Taken together, azoxystrobin and kresoxim‐methyl could be a good substitute for MBC or IBP for controlling rice blast in China, but should be carefully used as they were both at‐risk.     

Novel glyphosate-resistant aroA Gene from Paracoccus denitrificans in transgenic Arabidopsis

Applied Biochemistry and Microbiology - To date, only aroA variants derived from Agrobacterium tumefaciens CP4 have been used to generate the commercial glyphosate-resistant crops currently...     

Peroxisome Proliferator-activated Receptor-D (PPARD) Coordinates Mouse Spermatogenesis by Modulating Extracellular Signal-regulated Kinase (ERK)-dependent Signaling

Ppard^−/− mice exhibit smaller litter size compared with Ppard^+/+ mice. To determine whether peroxisome proliferator-activated receptor-D (PPARD) could possibly influence this phenotype, the role of PPARD in testicular biology was examined. Atrophic testes and testicular degeneration were observed in Ppard^−/− mice compared with Ppard^+/+ mice, indicating that PPARD modulates spermatogenesis. Higher expression of p27 and decreased expression of proliferating cellular nuclear antigen in Sertoli cells were observed in Ppard^+/+ mice as compared with Ppard^−/− mice, and these were associated with decreased Sertoli cell number in Ppard^+/+ mice. Cyclin D1 and cyclin D2 expression was lower in Ppard^+/+ as compared with Ppard^−/− mice. Ligand activation of PPARD inhibited proliferation of a mouse Sertoli cell line, TM4, and an inverse agonist of PPARD (DG172) rescued this effect. Temporal inhibition of extracellular signal-regulated kinase (ERK) activation by PPARD in the testis was observed in Ppard^+/+ mice and was associated with decreased serum follicle-stimulating hormone and higher claudin-11 expression along the blood-testis barrier. PPARD-dependent ERK activation also altered expression of claudin-11, p27, cyclin D1, and cyclin D2 in TM4 cells, causing inhibition of cell proliferation, maturation, and formation of tight junctions in Sertoli cells, thus confirming a requirement for PPARD in accurate Sertoli cell function. Combined, these results reveal for the first time that PPARD regulates spermatogenesis by modulating the function of Sertoli cells during early testis development.     

Marine Snails and Slugs: a Great Place To Look for Antiviral Drugs

Molluscs, comprising one of the most successful phyla, lack clear evidence of adaptive immunity and yet thrive in the oceans, which are rich in viruses. There are thought to be nearly 120,000 species of Mollusca, most living in marine habitats. Despite the extraordinary abundance of viruses in oceans, molluscs often have very long life spans (10 to 100 years). Thus, their innate immunity must be highly effective at countering viral infections. Antiviral compounds are a crucial component of molluscan defenses against viruses and have diverse mechanisms of action against a wide variety of viruses, including many that are human pathogens. Antiviral compounds found in abalone, oyster, mussels, and other cultured molluscs are available in large supply, providing good opportunities for future research and development. However, most members of the phylum Mollusca have not been examined for the presence of antiviral compounds. The enormous diversity and adaptations of molluscs imply a potential source of novel antiviral compounds for future drug discovery.