T cell exhaustion presents one of the major hurdles to cancer immunotherapy. Among exhausted CD8+ tumor-infiltrating lymphocytes, terminally subset contributes directly tumor killing owing its cytotoxic effector function. However, this does not respond immune checkpoint blockades and is difficult be reinvigorated with restored proliferative capacity. Here, we show that a half-life-extended inte...

Eukaryotic elongation factor 2 (eEF2) mediates translocation of peptidyl-tRNA from the ribosomal A site to P promote translational elongation. Its phosphorylation on Thr56 by its single known kinase eEF2K inactivates it and inhibits Extensive studies have revealed that different signal cascades modulate activity, but whether additional factors regulate eEF2 remains unclear. Here, we find X chro...

We demonstrated recently that organocatalysts, based on a nucleophilic core (N-alkylimidazole or 4-aminopyridine) and decorated with an extensive secondary-sphere envelope (connected to the through benzyl substituent), strongly affect site selectivity in acylation phosphorylation of amphiphilic diols, sometimes entirely overriding innate predisposition substrate. Preliminary studies pointed out...

In the present study we investigated participation of hepatic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) in metabolic programming newborn rats exposed utero to dexamethasone (DEX). On 21st day life, fasted offspring born DEX-treated mothers displayed increased conversion pyruvate into glucose with simultaneous upregulation PEPCK (phosphoenolpyruvate carboxykin...

Abstract Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet be clarified. We report this study that secretory ECM1a induces through GPR motif binding integrin ?X?2 and activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP cassette subfamily G member 1 (ABCG1) transduces ECM1a-integrin interactive si...

Individuals infected with human immunodeficiency virus type-1 (HIV-1) show metabolic alterations of CD4+ T cells through unclear mechanisms undefined consequences. We analyzed the transcriptome from patients HIV-1 and revealed that elevated oxidative phosphorylation (OXPHOS) pathway is associated poor outcomes. Inhibition OXPHOS by US Food Drug Administration–approved drug metformin, which targ...

Bullous pemphigoid-like epidermolysis bullosa acquisita (EBA) is an autoantibody-driven, granulocyte-mediated skin disease. The role of cellular metabolism and its potential as a therapeutic target in EBA are unknown.We investigated the effect 2-deoxy-D-glucose metformin antibody transfer model EBA. Both attenuated disease this model. Subsequently, we demonstrate that stimulation neutrophils by...

Abstract Innate-like T cells are unusual that enriched in mucosal tissues, where they constitute a prominent source of pro-inflammatory cytokines like IL-17 and IFN-γ. During thymic development, mouse γδ commit to either γδT1, γδT2, or γδT17 phenotypes through mechanisms remain unclear. Recent observations from our laboratory have suggested role for the SLAM/SAP signaling pathway cell developme...

Ethylene response factor proteins are important for regulating gene expression under different stresses. Different isoforms for ERF have previously isolated from bread wheat (Triticum aestivum L.) and related genera and called from TaERF1 to TaERF5. We isolated, cloned and molecular characterized a novel one based on TdERF1, an isoform in durum wheat (Tri...

1. The ability of 4,6-dinitrocresol and eight other substituted phenols to stimulate oxygen uptake and inhibit phosphorylation by a cell-free particulate system from unfertilized Arbacia eggs has been determined. Five of those agents can produce both stimulation of oxygen consumption and inhibition of phosphorylation; one inhibits both oxygen consumption and phosphorylation; and two have no eff...