Estimating the Spins of Stellar-Mass Black Holes by Fitting Their Continuum Spectra

We have used the Novikov-Thorne thin disk model to fit the continuum X-ray spectra of three transient black hole X-ray binaries in the thermal state. From the fits we estimate the dimensionless spin parameters of the black holes to be: 4U 1543-47, a* = a/M = 0.7-0.85; GRO J1655-40, a* = 0.65-0.8; GRS 1915+105, a* = 0.98-1. We plan to expand the sample of spin estimates to about a dozen over the next several years. Some unresolved theoretical issues are briefly discussed.Comment: 8 pages, 4 figures, 1 table; to appear in "Astrophysics of Compact Objects" eds. Y. F. Yuan, X. D. Li, D. Lai, AI

An Unconventional Glutamatergic Circuit in the Retina Formed by vGluT3 Amacrine Cells

SummaryIn the vertebrate retina, glutamate is traditionally thought to be released only by photoreceptors and bipolar cells to transmit visual signals radially along parallel ON and OFF channels. Lateral interactions in the inner retina are mediated by amacrine cells, which are thought to be inhibitory neurons. Here, we report calcium-dependent glutamate release from vGluT3-expressing amacrine cells (GACs) in the mouse retina. GACs provide an excitatory glutamatergic input to ON-OFF and ON direction-selective ganglion cells (DSGCs) and a subpopulation of W3 ganglion cells, but not to starburst amacrine cells. GACs receive excitatory inputs from both ON and OFF channels, generate ON-OFF light responses with a medium-center, wide-surround receptive field structure, and directly regulate ganglion cell activity. The results reveal a functional glutamatergic circuit that mediates noncanonical excitatory interactions in the retina and probably plays a role in generating ON-OFF responses, crossover excitation, and lateral excitation

TNF-insulin crosstalk at the transcription factor GATA6 is revealed by a model that links signaling and transcriptomic data tensors

Signal -transduction networks coordinate transcriptional programs activated by diverse extracellular stimuli, such as growth factors and cytokines. Cells receive multiple stimuli simultaneously, and mapping how activation of the integrated signaling network affects gene expression is a challenge. We stimulated colon adenocarcinoma cells with various combinations of the cytokine tumor necrosis factor (TNF) and the growth factors insulin and epidermal growth factor (EGF) to investigate signal integration and transcriptional crosstalk. We quantitatively linked the proteomic and transcriptomic data sets by implementing a structured computational approach called tensor partial least squares regression. This statistical model accurately predicted transcriptional signatures from signaling arising from single and combined stimuli and also predicted time-dependent contributions of signaling events. Specifically, the model predicted that an early-phase, Akt-associated signal downstream of insulin repressed a set of transcripts induced by TNF. Through bioinformatics and cell-based experiments, we identified the Akt-repressed signal as glycogen synthase kinase 3 (GSK3)–catalyzed phosphorylation of Ser37 on the long form of the transcription factor GATA6. Phosphorylation of GATA6 on Ser37 promoted its degradation, thereby preventing GATA6 from repressing transcripts that are induced by TNF and attenuated by insulin. Our analysis showed that predictive tensor modeling of proteomic and transcriptomic data sets can uncover pathway crosstalk that produces specific patterns of gene expression in cells receiving multiple stimuli

Dynamics of Trophoblast Differentiation in Peri-Implantation–Stage Human Embryos

Single-cell RNA sequencing of cells from cultured human blastocysts has enabled us to define the transcriptomic landscape of placental trophoblast (TB) that surrounds the epiblast and associated embryonic tissues during the enigmatic day 8 (D8) to D12 peri-implantation period before the villous placenta forms. We analyzed the transcriptomes of 3 early placental cell types, cytoTB (CTB), syncytioTB (STB), and migratoryTB (MTB), picked manually from cultured embryos dissociated with trypsin and were able to follow sublineages that emerged from proliferating CTB at the periphery of the conceptus. A unique form of CTB with some features of STB was detectable at D8, while mature STB was at its zenith at D10. A form of MTB with a mixed MTB/CTB phenotype arose around D10. By D12, STB generation was in decline, CTB had entered a new phase of proliferation, and mature MTB cells had begun to move from the main body of the conceptus. Notably, the MTB transcriptome at D12 indicated enrichment of transcripts associated with IFN signaling, migration, and invasion and upregulation of HLA-C, HLA-E, and HLA-G. The STB, which is distinct from the STB of later villous STB, had a phenotype consistent with intense protein export and placental hormone production, as well as migration and invasion. The studies show that TB associated with human embryos is in rapid developmental flux during periimplantation period when it must invade, signal robustly to the mother to ensure that the pregnancy continues, and make first contact with the maternal immune system

A Novel Mechanism of TRAF Signaling Revealed by Structural and Functional Analyses of the TRADD–TRAF2 Interaction

AbstractTRAF proteins are major mediators for the cell activation, cell survival, and antiapoptotic functions of the TNF receptor superfamily. They can be recruited to activated TNF receptors either by direct interactions with the receptors or indirectly via the adaptor protein TRADD. We now report the structure of the TRADD-TRAF2 complex, which is highly distinct from receptor–TRAF2 interactions. This interaction is significantly stronger and we show by an in vivo signaling assay that TRAF2 signaling is more readily initiated by TRADD than by direct receptor–TRAF2 interactions. TRADD is specific for TRAF1 and TRAF2, which ensures the recruitment of cIAPs for the direct inhibition of caspase activation in the signaling complex. The stronger affinity and unique specificity of the TRADD–TRAF2 interaction are crucial for the suppression of apoptosis and provide a mechanistic basis for the perturbation of TRAF recruitment in sensitizing cell death induction