The SWI/SNF ATP-Dependent Chromatin Remodeling Complex in Arabidopsis Responds to Environmental Changes in Temperature-Dependent Manner

SWI/SNF ATP-dependent chromatin remodeling complexes (CRCs) play important roles in the regulation of transcription, cell cycle, DNA replication, repair, and hormone signaling in eukaryotes. The core of SWI/SNF CRCs composed of a SWI2/SNF2 type ATPase, a SNF5 and two of SWI3 subunits is sufficient for execution of nucleosome remodeling in vitro. The Arabidopsis genome encodes four SWI2/SNF2 ATPases, four SWI3, a single SNF5 and two SWP73 subunits. Genes of the core SWI/SNF components have critical but not fully overlapping roles during plant growth, embryogenesis, and sporophyte development. Here we show that the Arabidopsis swi3c mutant exhibits a phenotypic reversion when grown at lower temperature resulting in partial restoration of its embryo, root development and fertility defects. Our data indicates that the swi3c mutation alters the expression of several genes engaged in low temperature responses. The location of SWI3C-containing SWI/SNF CRCs on the ICE1, MYB15 and CBF1 target genes depends on the temperature conditions, and the swi3c mutation thus also influences the transcription of several cold-responsive (COR) genes. These findings, together with genetic analysis of swi3c/ice1 double mutant and enhanced freezing tolerance of swi3c plants illustrate that SWI/SNF CRCs contribute to fine-tuning of plant growth responses to different temperature regimes

Evaluation of the role of downregulation of SNF5/INI1 core subunit of SWI/SNF complex in clear cell renal cell carcinoma development

Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau (VHL) gene. Additionally, in about 40% of ccRCC cases the mutation in PBRM1 (POLYBROMO1) gene coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found suggesting potential impairment of this complex function in ccRCC. In this study we assessed the extent to which the core SWI/SNF complex subunit - INI1 (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the development of this type of cancer. The evaluation of INI1 protein level in samples from 50 patients with diagnosed ccRCC, including three displaying rhabdoid features, showed the INI1 positive staining in rhabdoid cells while the conventional ccRCC cells exhibited reduced INI1 level. This indicated the rhabdoid component of ccRCC as distinct from other known rhabdoid tumors. The reduced INI1 protein level observed in all conventional ccRCC cases used in this study correlated with decreased SMARCB1 gene expression at the transcript level. Consistently, the overexpression of INI1 protein in A498 ccRCC cell line resulted in the elevation of endogenous SMARCB1 transcript level indicating that the INI1-dependent regulatory feedback loop controlling expression of this gene is affected in ccRCC Moreover, the set of INI1 target genes including i.e. CXCL12/CXCR7/CXCR4 chemokine axis was identified to be affected in ccRCC. In summary, we demonstrated that the inactivation of INI1 may be of high importance for ccRCC development and aggressiveness

Transition from Fireball to Poynting-flux-dominated Outflow in Three-Episode GRB 160625B

The ejecta composition is an open question in gamma-ray bursts (GRB) physics. Some GRBs possess a quasi-thermal spectral component in the time-resolved spectral analysis, suggesting a hot fireball origin. Others show a featureless non-thermal spectrum known as the "Band" function, consistent with a synchrotron radiation origin and suggesting that the jet is Poynting-flux-dominated at the central engine and likely in the emission region as well. There are also bursts showing a sub-dominant thermal component and a dominant synchrotron component suggesting a likely hybrid jet composition. Here we report an extraordinarily bright GRB 160625B, simultaneously observed in gamma-rays and optical wavelengths, whose prompt emission consists of three isolated episodes separated by long quiescent intervals, with the durations of each "sub-burst" being $\sim$ 0.8 s, 35 s, and 212 s, respectively. Its high brightness (with isotropic peak luminosity L$_{\rm p, iso}\sim 4\times 10^{53}$ erg/s) allows us to conduct detailed time-resolved spectral analysis in each episode, from precursor to main burst and to extended emission. The spectral properties of the first two sub-bursts are distinctly different, allowing us to observe the transition from thermal to non-thermal radiation between well-separated emission episodes within a single GRB. Such a transition is a clear indication of the change of jet composition from a fireball to a Poynting-flux-dominated jet.Comment: Revised version reflecting the referees' comments. 27 pages, 11 figures, 5 tables. The final edited version will appear in Nature Astronom

PD-L1 Overexpression, SWI/SNF Complex Deregulation, and Profound Transcriptomic Changes Characterize Cancer-Dependent Exhaustion of Persistently Activated CD4+ T Cells

Growing tumors avoid recognition and destruction by the immune system. During continuous stimulation of tumor-infiltrating lymphocytes (TILs) by tumors, TILs become functionally exhausted; thus, they become unable to kill tumor cells and to produce certain cytokines and lose their ability to proliferate. This collectively results in the immune escape of cancer cells. Here, we show that breast cancer cells expressing PD-L1 can accelerate exhaustion of persistently activated human effector CD4+ T cells, manifesting in high PD-1 and PD-L1 expression level son T cell surfaces, decreased glucose metabolism genes, strong downregulation of SWI/SNF chromatin remodelingcomplex subunits, and p21 cell cycle inhibitor upregulation. This results in inhibition of T cell proliferation and reduction of T cell numbers. The RNAseq analysis on exhausted CD4+ T cells indicated strong overexpression of IDO1 and genes encoding pro-inflammatory cytokines and chemokines. Some interleukins were also detected in media from CD4+ T cells co-cultured with cancer cells. The PD-L1 overexpression was also observed in CD4+ T cells after co-cultivation with other cell lines overexpressing PD-L1, which suggested the existence of a general mechanism of CD4+ T cell exhaustion induced by cancer cells. The ChIP analysis on the PD-L1 promoter region indicated that the BRM recruitment in control CD4+ T cells was replaced by BRG1 and EZH2 in CD4+ T cells strongly exhausted by cancer cells. These findings suggest that epi-drugs such as EZH2 inhibitors may be used as immunomodulators in cancer treatment

Transition from fireball to Poynting-flux-dominated outflow in the three-episode GRB 160625B

The ejecta composition is an open question in gamma-ray burst (GRB) physics . Some GRBs possess a quasi-thermal spectral component in the time-resolved spectral analysis , suggesting a hot fireball origin. Others show a featureless non-thermal spectrum known as the Band function , consistent with a synchrotron radiation origin and suggesting that the jet is Poynting-flux dominated at the central engine and probably in the emission region as well . There are also bursts showing a sub-dominant thermal component and a dominant synchrotron component , suggesting a probable hybrid jet composition . Here, we report an extraordinarily bright GRB 160625B, simultaneously observed in gamma-ray and optical wavelengths, whose prompt emission consists of three isolated episodes separated by long quiescent intervals, with the durations of each sub-burst being approximately 0.8 s, 35 s and 212 s, respectively. Its high brightness (with isotropic peak luminosity L ≈ 4 × 10 erg s) allows us to conduct detailed time-resolved spectral analysis in each episode, from precursor to main burst and to extended emission. The spectral properties of the first two sub-bursts are distinctly different, allowing us to observe the transition from thermal to non-thermal radiation between well-separated emission episodes within a single GRB. Such a transition is a clear indication of the change of jet composition from a fireball to a Poynting-flux-dominated jet.B.-B.Z. thanks Y.-Z. Fan, Y.-Z. Wang, H. Wang, K. D. Alexander and D. Lazzati for helpful discussions. We are grateful to K. Hurley, I. Mitrofanov, A. Sanin, M. Litvak and W. Boynton for the use of Mars Odyssey data in the triangulation. We acknowledge the use of the public data from the Swift and Fermi data archives. B.-B. Z. and A.J. C.-T. acknowledge support from the Spanish Ministry Projects AYA2012-39727-C03-01 and AYA2015-71718-R. Part of this work made use of B.-B.Z.'s personal Interactive Data Language (IDL) code library ZBBIDL and personal Python library ZBBPY. The computation resources used in this work are owned by Scientist Support LLC. B.Z. acknowledges NASA NNX14AF85G and NNX15AK85G for support. Z. G. D. acknowledges the National Natural Science Foundation of China(NSFC) (grant 11573014). Y.-D. H. acknowledges support by China Scholarships Council (grant 201406660015). Mini-MegaTORTORA belongs to Kazan Federal University, and the work is performed according to the Russian Government Program of Competitive Growth of Kazan Federal University. A. P., E.M., P. M. and A.V. are grateful to the Russian Foundation for Basic Research (grant 17-02-01388) for partial support. A. P. and S.B.P. acknowledge joint BRICS (Brazil, Russia, India, China and South Africa) grant RFBR 17-52-80139 and 388-ProFChEAP for partial support. R. I. is grateful to grant RUSTAVELI FR/379/6300/ 14 for partial support. Observations on Mini-MegaTORTORA are supported by the Russian Science Foundation (grant 14-50-00043). A.V.F. and A. M. thank the Russian Science Foundation (grant 14-50-00043). L.M. and A.F.Z. acknowledge support from INTA-CEDEA ESAt personnel hosting the Pi of the Sky facility at the BOOTES-1 station. H. G. and X.-Y.W. acknowledge NSFC (grants 11603003 and 11625312, respectively). Z. G. D., X.-F. W., B.Z., X.-Y. W.,L.S. and F.-W.Z. are also supported by the 973 program (grant 2014CB845800). F.-W.Z. is also supported in part by the NSFC (grants U1331101 and 11163003), the Guangxi Natural Science Foundation (grant 2013GXNSFAA019002) and the project of outstanding young teachers' training in higher education institutions of Guangxi. L.S. acknowledges support by the NSFC (grant 11103083) and the Joint NSFC-ISF Research Program (grant 11361140349). S.O. acknowledges the support of the Leverhulme Trust. S.J. acknowledges support from Korea Basic Science Research Program through NRF-2014R1A6A3A03057484 and NRF-2015R1D1A4A01020961, and I. H. P. through NRF-2015R1A2A1A01006870 and NRF-2015R1A2A1A15055344. R. A., D. F. and D. S. acknowledge support from RSF (grant 17-12-01378). A. K. acknowledges the Science and Education Ministry of Kazakhstan (grant 0075/GF4).Peer reviewe

Transition from fireball to Poynting-flux-dominated outflow in three-episode GRB 160625B [submitted version]

The ejecta composition of gamma-ray bursts (GRBs) is an open question in GRB physics. Some GRBs possess a quasi-thermal spectral component in the time-resolved spectral analysis, suggesting a hot fireball origin. Some others show an essentially feature-less non-thermal spectrum known as the "Band" function, which can be interpreted as synchrotron radiation in an optically thin region, suggesting a Poynting-flux-dominated jet composition. Here we report an extraordinarily bright GRB 160625B, simultaneously observed in gamma-rays and optical wavelengths, whose prompt emission consists of three dramatically different isolated episodes separated by long quiescent intervals, with the durations of each "sub-burst" being ∼ 0.8 s, 35 s, and 212 s, respectively. The high brightness (with isotropic peak luminosity Lp,iso∼4×1053 erg/s) of this GRB allows us to conduct detailed time-resolved spectral analysis in each episode, from precursor to the main burst and extended emission. Interestingly, the spectral properties of the first two sub-bursts are distinctly different, which allow us for the first time to observe the transition from thermal to non-thermal radiation in a single GRB. Such a transition is a clear indication of the change of jet composition from a fireball to a Poynting-flux-dominated jet

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams