Thromopoietin signaling to chromatin elicits rapid and pervasive epigenome remodeling within poised chromatin architectures.

Thrombopoietin (TPO) is a critical cytokine regulating hematopoietic stem cell maintenance and differentiation into the megakaryocytic lineage. However, the transcriptional and chromatin dynamics elicited by TPO signaling are poorly understood. Here, we study the immediate early transcriptional and cis-regulatory responses to TPO in hematopoietic stem/progenitor cells (HSPCs) and use this paradigm of cytokine signaling to chromatin to dissect the relation between cis- regulatory activity and chromatin architecture. We show that TPO profoundly alters the transcriptome of HSPCs, with key hematopoietic regulators being transcriptionally repressed within 30 minutes of TPO. By examining cis-regulatory dynamics and chromatin architectures, we demonstrate that these changes are accompanied by rapid and extensive epigenome remodeling of cis-regulatory landscapes that is spatially coordinated within topologically associating domains (TADs). Moreover, TPO-responsive enhancers are spatially clustered and engage in preferential homotypic intra- and inter-TAD interactions that are largely refractory to TPO signaling. By further examining the link between cis-regulatory dynamics and chromatin looping, we show that rapid modulation of cis-regulatory activity is largely independent of chromatin looping dynamics. Finally, we show that, although activated and repressed cis-regulatory elements share remarkably similar DNA sequence compositions, transcription factor binding patterns accurately predict rapid cis-regulatory responses to TPO

Egg on Hegranes: Geophysical Prospection, Coring, & Test Excavations—Report 2016

This report describes the 2016 archaeological work at the farm of Egg is in the southernmost part of Hegranes, North Iceland

INTEGRAL-RXTE observations of Cygnus X-1

We present first results from contemporaneous observations of Cygnus X-1 with INTEGRAL and RXTE, made during INTEGRAL's performance verification phase in 2002 November and December. Consistent with earlier results, the 3-250 keV data are well described by Comptonization spectra from a Compton corona with a temperature of kT~50-90 keV and an optical depth of tau~1.0-1.3 plus reflection from a cold or mildly ionized slab with a covering factor of Omega/2pi~0.2-0.3. A soft excess below 10 keV, interpreted as emission from the accretion disk, is seen to decrease during the 1.5 months spanned by our observations. Our results indicate a remarkable consistency among the independently calibrated detectors, with the remaining issues being mainly related to the flux calibration of INTEGRAL.Comment: 6 pages, 3 figures. Figs. 2 and 3 are best viewed in color. Accepted for publication in the INTEGRAL special edition of A&A

Multifrequency Observations of the Virgo Blazars 3C 273 and 3C 279 in CGRO Cycle 8

We report first observational results of multifrequency campaigns on the prominent Virgo blazars 3C 273 and 3C 279 which were carried out in January and February 1999. Both blazars are detected from radio to gamma-ray energies. We present the measured X- to gamma-ray spectra of both sources, and for 3C 279 we compare the 1999 broad-band (radio to gamma-ray) spectrum to measured previous ones.Comment: 5 pages including 3 figures, latex2e, to appear in: 'Proc. of the 5th Compton Symposium', AIP, in pres

Estrogens Determine Adherens Junction Organization and E-Cadherin Clustering in Breast Cancer Cells via Amphiregulin

Estrogens play an important role in the development and progression of human cancers, particularly in breast cancer. Breast cancer progression depends on the malignant destabilization of adherens junctions (AJs) and disruption of tissue integrity. We found that estrogen receptor alpha (ER alpha) inhibition led to a striking spatial reorganization of AJs and microclustering of E-Cadherin (E-Cad) in the cell membrane of breast cancer cells. This resulted in increased stability of AJs and cell stiffness and a reduction of cell motility. These effects were actomyosindependent and reversible by estrogens. Detailed investigations showed that the ERa target gene and epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) essentially regulates AJ reorganization and E-Cad microclustering. Our results not only describe a biological mechanism for the organization of AJs and the modulation of mechanical properties of cells but also provide a new perspective on how estrogens and anti-estrogens might influence the formation of breast tumors

A Mass Model for Estimating the Gamma Ray Background of the Burst and Transient Source Experiment

Orbiting x-ray and gamma ray instruments are subject to large background count rates due to local particle fluxes in the space environment. The ability of an instrument to make calibrated measurements of the flux from a source of interest is highly dependent on accurately determining the background level. We present here a method of calculating the energy dependent background flux for any point in the complete data set recorded by the Burst and Transient Source Experiment (BATSE) in its nine year mission. The BATSE Mass Model (BAMM) uses a Monte Carlo mass modelling approach to produce a data base of the gamma ray background which is then filtered to simulate the background count rate with a 2.048 second time resolution. This method is able to reduce the variations in the background flux by a factor of 8 - 10, effectively `flat-fielding' the detector response. With flat-fielded BATSE data it should be possible to use the Earth occultation technique to produce a hard x-ray all sky survey to the 1-2 mCrab sensitivity limit. BAMM is also capable of estimating the contribution to the spectra measured from gamma ray sources due to the reprocessing of source photons in inactive material surrounding a gamma ray detector. Possible applications of this aspect of the model in the area of Gamma Ray Burst spectral analysis are discussed.Comment: 11 pages, 9 figures. Accepted for publication in Astronomy and Astrophysics. Figures have been reduced to conform to astro-ph standard