A TNF‐p100 pathway subverts noncanonical NF‐κB signaling in inflamed secondary lymphoid organs

Lymphotoxin‐beta receptor (LTβR) present on stromal cells engages the noncanonical NF‐κB pathway to mediate RelB‐dependent expressions of homeostatic chemokines, which direct steady‐state ingress of naïve lymphocytes to secondary lymphoid organs (SLOs). In this pathway, NIK promotes partial proteolysis of p100 into p52 that induces nuclear translocation of the RelB NF‐κB heterodimers. Microbial infections often deplete homeostatic chemokines; it is thought that infection‐inflicted destruction of stromal cells results in the downregulation of these chemokines. Whether inflammation per se also regulates these processes remains unclear. We show that TNF accumulated upon non‐infectious immunization of mice similarly downregulates the expressions of these chemokines and consequently diminishes the ingress of naïve lymphocytes in inflamed SLOs. Mechanistically, TNF inactivated NIK in LTβR‐stimulated cells and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity as inhibitory IκBδ. Finally, a lack of p100 alleviated these TNF‐mediated inhibitions in inflamed SLOs of immunized Nfkb2^?/? mice. In sum, we reveal that an inhibitory TNF‐p100 pathway modulates the adaptive compartment during immune responses.     

Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis

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Responses of <Emphasis Type="Italic">Zea mays</Emphasis> L. cultivars ‘Buland’ and ‘Prakash’ to an antiozonant ethylene diurea grown under ambient and elevated levels of ozone

Increase in surface level of ozone (O₃) in last 30 years is one of the major problems for global agriculture. Field experiment was conducted using open top chambers on two Indian maize cultivars (Buland and Prakash) grown under ambient (AO) and elevated (EO) O₃ concentrations to evaluate the effect of an antiozonant ethylene diurea (EDU) given as soil drench. EDU application reduced the ROS production with concomitant decrease in lipid peroxidation. Inductions in activities of enzymatic antioxidants along with increased content of non-enzymatic antioxidants were observed in EDU-treated plants, though the response varied between the cultivars. Photosynthetic proteins (PEP carboxylase and RuBisCO large and small subunits) detected through SDS–PAGE analysis increased with EDU treatment. EDU also led to an increase in jasmonic acid and a decline in salicylic acid contents. The protective effect of EDU was further accompanied by increased pigments (chlorophyll and carotenoids), foliar carbohydrates (starch and total soluble sugars), enhanced biomass, and economic yield. Effectiveness of EDU was more evident at higher O₃ concentration and cultivar Prakash exhibited a more positive response with EDU as compared to Buland.     

Novel polysaccharide produced by Azotobacter vinelandii isolated from plant rhizosphere

Summary A strain of Azotobacter vinelandii MTCC 2460 has been isolated from the rhizosphere of the rhizomes of lotus, which produces a novel exopolysaccharide (EPS) having a sugar composition of glucose : galactose : fucose: glucoronic acid (2.2 : 2.7 : 5.6 : 1.6). This composition has not been reported for any species belonging to this genus. The EPS gives high viscosity comparable to xanthan under specific conditions.     

Receptor Activity-modifying Proteins 2 and 3 Generate Adrenomedullin Receptor Subtypes with Distinct Molecular Properties

Adrenomedullin (AM) is a peptide hormone with numerous effects in the vascular systems. AM signals through the AM₁ and AM₂ receptors formed by the obligate heterodimerization of a G protein-coupled receptor, the calcitonin receptor-like receptor (CLR), and receptor activity-modifying proteins 2 and 3 (RAMP2 and RAMP3), respectively. These different CLR-RAMP interactions yield discrete receptor pharmacology and physiological effects. The effective design of therapeutics that target the individual AM receptors is dependent on understanding the molecular details of the effects of RAMPs on CLR. To understand the role of RAMP2 and -3 on the activation and conformation of the CLR subunit of AM receptors, we mutated 68 individual amino acids in the juxtamembrane region of CLR, a key region for activation of AM receptors, and determined the effects on cAMP signaling. Sixteen CLR mutations had differential effects between the AM₁ and AM₂ receptors. Accompanying this, independent molecular modeling of the full-length AM-bound AM₁ and AM₂ receptors predicted differences in the binding pocket and differences in the electrostatic potential of the two AM receptors. Druggability analysis indicated unique features that could be used to develop selective small molecule ligands for each receptor. The interaction of RAMP2 or RAMP3 with CLR induces conformational variation in the juxtamembrane region, yielding distinct binding pockets, probably via an allosteric mechanism. These subtype-specific differences have implications for the design of therapeutics aimed at specific AM receptors and for understanding the mechanisms by which accessory proteins affect G protein-coupled receptor function.     

Effect of cytosol on transport of RNA in vitro during cardiac hypertrophy.

An enhanced RNA-transport activity was observed in vitro from nuclei obtained from animals with cardiac hypertrophy as compared with that of sham-operated controls. The 100 000 g supernatants obtained from hypertrophic hearts stimulated the RNA transport from nuclei of sham-operated controls, and this stimulation was maximum with 40% supernatant. Ca2+- and nucleic acid-dependent ATPase and alkaline phosphatase activities, which may be involved in an energy-dependent transport, were high in nuclei from hypertrophic hearts, and the nuclei of sham-operated animals showed higher activities of these enzymes after incubation with supernatant from hypertrophic hearts, which stimulates the RNA transport in vitro from nuclei of sham-operated animals.