Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol

© 2017 The Author(s). Toll-like receptors (TLRs) are major players of the innate immune system. Once activated, they trigger a signalling cascade that leads to NF-ΰ B translocation from the cytoplasm to the nucleus. Single cell analysis shows that NF-ΰ B signalling dynamics are a critical determinant of transcriptional regulation. Moreover, the outcome of innate immune response is also affected by the cross-talk between TLRs and estrogen signalling. Here, we characterized the dynamics of TLR5 signalling, responsible for the recognition of flagellated bacteria, and those changes induced by estradiol in its signalling at the single cell level. TLR5 activation in MCF7 cells induced a single and sustained NF-k B translocation into the nucleus that resulted in high NF-k B transcription activity. The overall magnitude of NF-k B transcription activity was not influenced by the duration of the stimulus. No significant changes are observed in the dynamics of NF-k B translocation to the nucleus when MCF7 cells are incubated with estradiol. However, estradiol significantly decreased NF-k B transcriptional activity while increasing TLR5-mediated AP-1 transcription. The effect of estradiol on transcriptional activity was dependent on the estrogen receptor activated. This fine tuning seems to occur mainly in the nucleus at the transcription level rather than affecting the translocation of the NF-k B transcription factor

Temperature regulates NF-κB dynamics and function through timing of A20 transcription

NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate–controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation

SN 2016coi/ASASSN-16fp: An example of residual helium in a type Ic supernova?

The optical observations of Ic-4 supernova (SN) 2016coi/ASASSN-16fp, from $\sim 2$ to $\sim450$ days after explosion, are presented along with analysis of its physical properties. The SN shows the broad lines associated with SNe Ic-3/4 but with a key difference. The early spectra display a strong absorption feature at $\sim 5400$ \AA\ which is not seen in other SNe~Ic-3/4 at this epoch. This feature has been attributed to He I in the literature. Spectral modelling of the SN in the early photospheric phase suggests the presence of residual He in a C/O dominated shell. However, the behaviour of the He I lines are unusual when compared with He-rich SNe, showing relatively low velocities and weakening rather than strengthening over time. The SN is found to rise to peak $\sim 16$ d after core-collapse reaching a bolometric luminosity of Lp $\sim 3\times10^{42}$ \ergs. Spectral models, including the nebular epoch, show that the SN ejected $2.5-4$ \msun\ of material, with $\sim 1.5$ \msun\ below 5000 \kms, and with a kinetic energy of $(4.5-7)\times10^{51}$ erg. The explosion synthesised $\sim 0.14$ \msun\ of 56Ni. There are significant uncertainties in E(B-V)host and the distance however, which will affect Lp and MNi. SN 2016coi exploded in a host similar to the Large Magellanic Cloud (LMC) and away from star-forming regions. The properties of the SN and the host-galaxy suggest that the progenitor had $M_\mathrm{ZAMS}$ of $23-28$ \msun\ and was stripped almost entirely down to its C/O core at explosion.Comment: Accepted for publication in MNRAS. Updated to reflect the published version, minor typographical changes onl

Carnegie Supernova Project-II: The Near-infrared Spectroscopy Program

Shifting the focus of Type Ia supernova (SN Ia) cosmology to the near-infrared (NIR) is a promising way to significantly reduce the systematic errors, as the strategy minimizes our reliance on the empirical width-luminosity relation and uncertain dust laws. Observations in the NIR are also crucial for our understanding of the origins and evolution of these events, further improving their cosmological utility. Any future experiments in the rest-frame NIR will require knowledge of the SN Ia NIR spectroscopic diversity, which is currently based on a small sample of observed spectra. Along with the accompanying paper, Phillips et al. (2018), we introduce the Carnegie Supernova Project-II (CSP-II), to follow up nearby SNe Ia in both the optical and the NIR. In particular, this paper focuses on the CSP-II NIR spectroscopy program, describing the survey strategy, instrumental setups, data reduction, sample characteristics, and future analyses on the data set. In collaboration with the Harvard-Smithsonian Center for Astrophysics (CfA) Supernova Group, we obtained 661 NIR spectra of 157 SNe Ia. Within this sample, 451 NIR spectra of 90 SNe Ia have corresponding CSP-II follow-up light curves. Such a sample will allow detailed studies of the NIR spectroscopic properties of SNe Ia, providing a different perspective on the properties of the unburned material, radioactive and stable nickel produced, progenitor magnetic fields, and searches for possible signatures of companion stars.Comment: 20 pages, 7 figures, accepted for publication in PAS

LSQ13ddu: a rapidly evolving stripped-envelope supernova with early circumstellar interaction signatures

This paper describes the rapidly evolving and unusual supernova LSQ13ddu, discovered by the La Silla-QUEST survey. LSQ13ddu displayed a rapid rise of just 4.8 ± 0.9 d to reach a peak brightness of −19.70 ± 0.02 mag in the LSQgr band. Early spectra of LSQ13ddu showed the presence of weak and narrow HeI features arising from interaction with circumstellar material (CSM). These interaction signatures weakened quickly, with broad features consistent with those seen in stripped-envelope SNe becoming dominant around two weeks after maximum. The narrow HeI velocities are consistent with the wind velocities of luminous blue variables but its spectra lack the typically seen hydrogen features. The fast and bright early light curve is inconsistent with radioactive ⁵⁶Ni powering but can be explained through a combination of CSM interaction and an underlying ⁵⁶Ni decay component that dominates the later time behaviour of LSQ13ddu. Based on the strength of the underlying broad features, LSQ13ddu appears deficient in He compared to standard SNe Ib