ON THE COVER
Ablain et al. uncouple the effects of retinoids on transcription and differentiation from degradation of RARA and PML/RARA in acute promyelocytic leukemia (APL). The authors show that differentiation is insufficient for APL eradication, whereas PML/RARA loss is essential. Cover immunofluorescence image depicts bone marrow cells with nuclear PML/RARA micro-speckles (green).
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Brief Definitive Report
Uncoupling RARA transcriptional activation and degradation clarifies the bases for APL response to therapies
Synthetic retinoids activate RARA- or PML/RARA-dependent transcription, but fail to degrade RARA or PML/RARA protein, which is insufficient for eradication of acute promyelocytic leukemia.
Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies
Eliminating key glycosylation sites on HIV envelope (Env) restores binding of the germline versions of known broadly neutralizing anti-Env antibodies.
RhoGEF12 controls cardiac remodeling by integrating G protein– and integrin-dependent signaling cascades
RhoGEF12 is required for stretch-induced RhoA activation, and its absence protects mice against overload-induced heart failure.
The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development
The thymic medulla and an intact mTEC compartment are needed for the development of nTreg cells and negative selection of conventional T cells but not their further maturation.
Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength
Jagged2 preferentially signals through Notch3 to promote γδ T cell development.
In vivo fate mapping identifies pre-TCRα expression as an intra- and extrathymic, but not prethymic, marker of T lymphopoiesis
A novel pre-TCRα (pTα) reporter mouse reveals that expression of pTα is confined to the T lineage and does not occur on prethymic progenitors.
Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27–CD70 pathway
CD27–CD70 signals are required for optimal development of natural regulatory T cells from the thymus.
CD1c tetramers detect ex vivo T cell responses to processed phosphomycoketide antigens
CD1c tetramers loaded with a phospholipid antigen from M. tuberculosis are recognized by human T cells.
Systemic 4-1BB activation induces a novel T cell phenotype driven by high expression of Eomesodermin
Anti–4-1BB treatment of tumor-bearing or intracellular pathogen infected mice generates a population of Eomes+KLRG1+ tumor infiltrating T cells that have enhanced cytotoxic activity.
PD-1 promotes immune exhaustion by inducing antiviral T cell motility paralysis
PD-L1 decreases anti-viral CD8+ T cell motility and PD-1 blockade restores motility in the presence of high viral loads.
Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance
Lung-resident antigen-presenting macrophages promote tolerance to inhaled antigens via the induction of regulatory T cells.
miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma
miR-612 suppresses local invasion and distant colonization by directly inhibiting AKT2 in HCC.
O-acetylated N-acetylneuraminic acid as a novel target for therapy in human pre-B acute lymphoblastic leukemia
Removal of 9-O-acetyl residues from the cell surface N-acetylneuraminic acid makes ALL cells drug sensitive.
Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice
Reduction of the CHOP target Gadd34 restores motor function in P0S63del mice with demyelinating neuropathy.
Plasma glutamate–modulated interaction of A2AR and mGluR5 on BMDCs aggravates traumatic brain injury–induced acute lung injury
Activation of adenosine A2A receptor aggravates lung damage in a neurogenic mouse model of acute lung injury (ALI) but protects against nonneurogenic ALI.