We investigate the relationship between the linewidths of broad Mg II λ2800 and Hβ in active galactic nuclei (AGNs) to refine them as tools to estimate black hole (BH) masses. We perform a detailed spectral analysis of a large sample of AGNs at intermediate redshifts selected from the Sloan Digital Sky Survey, along with a smaller sample of archival ultraviolet spectra for nearby sources monitored with reverberation mapping (RM). Careful attention is devoted to accurate spectral decomposition, especially in the treatment of narrow-line blending and Fe II contamination. We show that, contrary to popular belief, the velocity width of Mg II tends to be smaller than that of Hβ, suggesting that the two species are not cospatial in the broad-line region. Using these findings and recently updated BH mass measurements from RM, we present a new calibration of the empirical prescriptions for estimating virial BH masses for AGNs using the broad Mg II and Hβ lines. We show that the BH masses derived from our new formalisms show subtle but important differences compared to some of the mass estimators currently used in the literature.
Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors1,2. Phagocytosis by macrophages plays a critical role in cancer control3–6. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo7–10, suggesting that blockade of the SIRPα–CD47 checkpoint could be useful in treating human cancer11–14. However, the prophagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely unknown. Here we find that macrophages are much more efficient at phagocytosis of haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in response to SIRPα–CD47 blockade. Using a mouse lacking the signalling lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell-specific receptors, we determined that phagocytosis of haematopoietic tumour cells during SIRPα–CD47 blockade was strictly dependent on SLAM family receptors in vitro and in vivo. In both mouse and human cells, this function required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319), expressed on macrophages and tumour cell targets. In contrast to most SLAM receptor functions15–17, SLAMF7-mediated phagocytosis was independent of signalling lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18–20) and utilize signals involving immunoreceptor tyrosine-based activation motifs21,22. These findings elucidate the mechanism by which macrophages engulf and destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor-independent function for a SLAM receptor. Lastly, they suggest that patients with tumours expressing SLAMF7 are more likely to respond to SIRPα–CD47 blockade therapy.
Ultrasmall PEGylated Cu Se nanoparticles with strong near-infrared absorption have been prepared by an ambient aqueous method. The resultant water-soluble and biocompatible nanoparticles are demonstrated to be a novel nanotheranostic agent for effective deep-tissue photoacoustic imaging, computed tomography imaging, single-photon emission computed tomography imaging, and photothermal therapy of cancer.
EAT-2 is an adaptor expressed in innate immune cells, including natural killer (NK) cells. It is closely related to the adaptor SAP, which regulates signaling lymphocyte activation molecule (SLAM)-related receptors by recruiting the kinase FynT to the receptors. Here we have studied the function of EAT-2 in NK cells by creating mice lacking or overexpressing EAT-2. Like SAP, EAT-2 was associated with the SLAM-related receptor 2B4 in NK cells. However, unlike SAP, EAT-2 was an inhibitor of NK cell function. EAT-2 repressed natural cytotoxicity and interferon-gamma secretion by a mechanism involving tyrosine phosphorylation of its C terminus. We have demonstrated a similar function for the adaptor ERT, a newly identified SAP family member expressed in mouse NK cells. These data identify a previously unknown mechanism of NK cell inhibition. Moreover, they indicate that EAT-2 and SAP have distinct and at times opposing functions in natural immunity.
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