The Quiescent Intracluster Medium in the Core of the Perseus Cluster

Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Constitutive Activation of the Canonical NF-κB Pathway Leads to Bone Marrow Failure and Induction of Erythroid Signature in Hematopoietic Stem Cells

Summary: Constitutive activation of the canonical NF-κB pathway has been associated with a variety of human pathologies. However, molecular mechanisms through which canonical NF-κB affects hematopoiesis remain elusive. Here, we demonstrate that deregulated canonical NF-κB signals in hematopoietic stem cells (HSCs) cause a complete depletion of HSC pool, pancytopenia, bone marrow failure, and premature death. Constitutive activation of IKK2 in HSCs leads to impaired quiescence and loss of function. Gene set enrichment analysis (GSEA) identified an induction of “erythroid signature” in HSCs with augmented NF-κB activity. Mechanistic studies indicated a reduction of thrombopoietin (TPO)-mediated signals and its downstream target p57 in HSCs, due to reduced c-Mpl expression in a cell-intrinsic manner. Molecular studies established Klf1 as a key suppressor of c-Mpl in HSPCs with increased NF-κB. In essence, these studies identified a previously unknown mechanism through which exaggerated canonical NF-κB signals affect HSCs and cause pathophysiology. : Nakagawa and Rathinam demonstrate that constitutive activation of IKK2 in HSCs causes a complete depletion of the HSC pool and impairs HSC functions due to a loss of “stemness” signature and an induction of erythroid signature. Keywords: self-renewal, hematopoietic stem cells, NF-kB, signal transduction, transcription factors, pancytopenia, bone marrow failure, erythroid differentiatio

A20 deficiency in multipotent progenitors perturbs quiescence of hematopoietic stem cells

Inflammatory signals have been shown to play a critical role in controlling the maintenance and functions of hematopoietic stem cells (HSCs). While the significance of inflammation in hematopoiesis has begun to unfold, molecular mechanisms and players that govern this mode of HSC regulation remain largely unknown. The E3 ubiquitin ligase A20 has been considered as a central gatekeeper of inflammation. Here, we have specifically depleted A20 in multi-potent progenitors (MPPs) and studied its impact on hematopoiesis. Our data suggest that lack of A20 in Flt3+ progenitors causes modest alterations in hematopoietic differentiation. Analysis of hematopoietic stem and progenitor cell (HSPC) pool revealed alterations in HSPC subsets including, HSCs, MPP1, MPP2, MPP3 and MPP4. Interestingly, A20 deficiency in MPPs caused loss of HSC quiescence and compromised long-term hematopoietic reconstitution. Mechanistic studies identified that A20 deficiency caused elevated levels of Interferon-γ signaling and downregulation of p57 in HSCs. In essence, these studies identified A20 as a key regulator of HSC quiescence and cell fate decisions

Germline DDX41 mutations define a unique subtype of myeloid neoplasms

: Germline DDX41 variants have been implicated in late-onset myeloid neoplasms (MNs). Despite an increasing number of publications, many important features of DDX41-mutated MNs remain to be elucidated. Here, enrolling a total of 346 patients with DDX41 pathogenic/likely pathogenic (P/LP) germline variants and/or somatic mutations from 9,082 MN patients, together with 525 first-degree relatives of DDX41-mutated and wild-type (WT) patients, we performed a comprehensive characterization of DDX41-mutated MNs. P/LP DDX41 germline variants explained ~80% of known germline predisposition to MNs in adults. These risk variants were 10-fold more enriched in Japanese MN cases (n=4,461) compared to a Japanese general population (n=20,238). This enrichment of DDX41 risk alleles was much more prominent in male than female (20.7 vs. 5.0). P/LP DDX41 variants conferred a large risk of developing MNs, which was negligible until 40 years old but rapidly increased to 49% by 90 years of age. DDX41-mutated MDS patients rapidly progressed to AML, which was, however, confined to those having truncating variants. Co-mutation patterns at diagnosis and at progression to AML were substantially different between DDX41-mutated and -WT cases, where none of the co-mutations affected clinical outcomes. Even TP53 mutations made no exceptions and their dismal effect, including multi-hit allelic status, on survival was almost completely mitigated by the presence of DDX41 mutations. Finally, outcomes were not affected by the conventional risk stratifications including the revised/molecular International Prognostic Scoring System (IPSS-R/M). Our findings establish that DDX41-mutated MDS defines a unique subtype of MNs that is distinct from other MNs

Detection of polarized gamma-ray emission from the Crab nebula with the Hitomi Soft Gamma-ray Detector

International audienceWe present the results from the Hitomi Soft Gamma-ray Detector (SGD) observation of the Crab nebula. The main part of SGD is a Compton camera, which in addition to being a spectrometer, is capable of measuring polarization of gamma-ray photons. The Crab nebula is one of the brightest X-ray/gamma-ray sources on the sky, and the only source from which polarized X-ray photons have been detected. SGD observed the Crab nebula during the initial test observation phase of Hitomi. We performed data analysis of the SGD observation, SGD background estimation, and SGD Monte Carlo simulations, and successfully detected polarized gamma-ray emission from the Crab nebula with only about 5 ks exposure time. The obtained polarization fraction of the phase-integrated Crab emission (sum of pulsar and nebula emissions) is (22.1% ± 10.6%), and the polarization angle is |${110{^{\circ}_{.}}7}$| +|${13{^{\circ}_{.}}2}$|/−|${13{^{\circ}_{.}}0}$| in the energy range of 60–160 keV (the errors correspond to the 1 σ deviation). The confidence level of the polarization detection was 99.3%. The polarization angle measured by SGD is about one sigma deviation with the projected spin axis of the pulsar, |${124{^{\circ}_{.}}0}$| ± |${0{^{\circ}_{.}}1}$|⁠