Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Unraveling the Effect of Differentially Applied Manganese on Root Dynamics and Efficiency of Diverse Rice Genotypes

Increasing manganese (Mn) deficiency in soils emphasizes strategies for breeding genotypes with increased Mn efficiency. The present investigation evaluated Mn efficiency of 11 rice genotypes w.r.t. basal, foliar, and basal+foliar Mn application in field and glasshouse conditions. The genotypes with B + F application had higher leaf area (LA), SPAD index, root length (RL), root surface area (RSA) and mean half distance between roots (MHDR), and ultimately higher Mn efficiency under both growing conditions. The results of correlation analysis depicted strong positive relation between grain yield and LA (0.60) and SPAD index (0.53). The root characteristics viz., RL, RSA, and MHDR could, respectively, explain 76%, 77%, and 83% of variation in grain yield emphasizing the importance of superior root geometry in regulating mechanism pertaining to differential Mn efficiency. The breeders could select the traits for better root geometry along with high yield in breeding programs to develop Mn efficient genotypes.