The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

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

Molecular and functional evaluation of bovine in vitro produced embryos vitrified by Cryotop Method

Tese (doutorado)—Universidade de Brasília, Faculdade de Agronomia e Medicina Veterinária, 2017.O sucesso da criopreservação de embriões bovinos é essencial para melhor aproveitamento de embriões produzidos em excesso, para o estabelecimento de bancos de germoplasma e para comercialização de genética. Neste estudo, foi analisada a alteração na expressão de genes induzida pelo procedimento de vitrificação por Cryotop em blastocistos bovinos usando lâminas de microarranjo EmbryoGENE. Embriões bovinos produzidos in vitro em estágio de blastocisto (144 a 156 horas pós-inseminação) foram vitrificados com Cryotop e não vitrificados (controle). Após 4 horas de cultivo, embriões que re-expandiram ou evoluíram para o estágio de blastocisto expandido foram usados para análises do microarranjo e para quantificação em reação de cadeia de polimerase em tempo real (qPCR). As análises da expressão global revelaram 43 genes diferencialmente expressos em embriões vitrificados comparados aos do grupo controle (p0,05), afeta a produção de blastocistos e também a resposta à criopreservação (p<0,05). E ainda, que os touros que produzem embriões mais crioresistentes nem sempre são os que produzem maior taxa de embriões PIV. Além disso, embriões macho e fêmea têm a mesma capacidade de resposta à vitrificação por Cryotop.The cryopreservation success of bovine embryos is essential for the better use of excess produced embryos, for the establishment of germplasm banks and genetics commercialization. In this study, gene expression alteration induced by the Cryotop vitrification procedure in bovine blastocysts using EmbryoGENE microarray slides was analyzed. Bovine in vitro produced embryos at blastocyst stage (144 to 156 hours postinsemination) were vitrified with Cryotop and non-vitrified (control). After 4 hours of culture, re-expanded or expanded blastocyst stage embryos were submitted to microarray analyzes and real time polymerase chain reaction (qPCR) quantification. Global gene expression analysis revealed 43 differentially expressed genes in vitrified embryos compared to control group (p <0.05). Nine genes in total were evaluated by qPCR, of which FOSL1, involved in apoptosis process, showed differential expression (p <0.05) for both methods, being overexpressed in vitrified embryos. The results suggest that apoptosis plays a key role in embryos response of vitrification process. Considering that vitrification response is closely related to embryo quality, it was hypothesized that embryos selection for vitrification could also influence the difference in male:female ratio due to developmental speed and stress tolerance. Therefore, in the second stage of this study, the bull´s influence on embryo developmental kinetics and embryo response to cryopreservation was evaluated. For this, five bulls were taken and embryos cryopreservation by Cryotop method was compared in addition to embryo production. Initially, blastocyst stage embryos were vitrified (144 to 156 hours post-insemination), to evaluate the cryotolerance relative to the bulls; while expanded blastocyst stage embryos were removed from culture at D6, D7 and D8, then sexed for developmental kinetics. As a second experiment, expanded blastocyst stage embryos were vitrified (168 hours post-insemination). All embryos (re-expanded, hatched blastocyst stage e, and degenerated) of both treatments, with 24 hours post-vitrification culture were used for sexing. The results suggest that sire´s choice, although not interfering in embryonic development kinetics, affects the blastocysts rates and the cryopreservation response. Besides, bulls producing more cryoresistent embryos are not always the ones that produce the highest IVP embryo rate. In addition, male and female embryos have the same Cryotop vitrification response

Clinical and Biological Implications of CUX1 Mutations in Myeloid Neoplasms

Abstract Recurrent somatic mutations of CUX1 are described in myeloid neoplasms. CUX1 is located at chromosome 7q22.1; -7/del(7q) involving CUX1 locus are common abnormalities in myelodysplastic syndromes (MDS). Mutations and loss of heterozygosity involving CUX1 have been also described in breast, lung and uterine cancers. Preliminary functional studies, lack of a mutational hotspot and coincidental deletions suggest loss of function/hypomorphic consequences of these molecular defects. CUX1 (p200), contains 4 evolutionarily conserved DNA-binding domains, including 3 CUT repeats and a CUT homeodomain. Functionally, CUX1 regulates many genes involved in DNA replication and chromosome segregation. Cell-based assays have established a role for CUX1 in the control of cell-cycle progression, cell motility, and invasion .The objective of this study is to assess the molecular context and clinical significance of CUX1 mutations and deletions in myeloid neoplasms. We analyzed a subset of 1478 patients [24% lower-risk MDS, 17% higher-risk MDS, 22% primary (p)AML, 14% secondary AML, 14% MDS/myeloproliferative neoplasms (MPN) and 9% MPN] for the presence of CUX1 mutations and deletions. No CUX1 mutations were found in core binding factor AML. We correlated the presence of these lesions with clinical parameters, cytogenetic abnormalities, and molecular features including clonal architecture and associated somatic mutations. Copy number variation and their boundaries were analyzed by Single Nucleotide Polymorphism (SNP) arrays and mutations by multiamplicon deep sequencing utilizing a panel targeting 60 most commonly mutated genes in myeloid neoplasms. In total cohort 4 % of patients had CUX1 mutations and 6% had locus deletions (affecting ch 7q commonly deleted region: 7q22.1) including 90% of del (7q) cases. Expression of CUX1 is significantly lower in AML with -7/del(7q) compared to AML with normal cytogenetics (p<.00001) and also in MDS with -7/del(7q) compared tohealthy controls (p=.004). Additionally, decreased expression of CUX1 was found in 15% of MDS and 8% of AML patients without -7/del(7q) or related mutations. Cases with lower expression had worse OS compared to patients with higher expression (p=.002). In terms of configuration, most mutations were heterozygous, 5% of mutations were hemizygous and 4% were homozygous (due to UPD). Among 75 somatic CUX1mutations; 72% were missense, 20% where frame shift and 8% where non sense. CUX1 mutations were associated with either lower-risk MDS (p=.0001) and pAML (p=.04) while deletions involving the CUX1 locus were significantly related to higher-risk MDS (p=.05). Heterozygous CUX1 mutations were more commonly associated with normal cytogenetics (p=.01). Patients with -7/del(7q) frequently represented del(5q) (p=.04) and thrombocytopenia (p=.001). The OS of patients with CUX1 mutations was shorter (p=.04) as was that of patients with CUX1/deletions (p=.02) when compared to wild type. We subsequently studied the molecular background of CUX1 alterations. CUX1 mutations (vs. wild type) were associated with TET2 (31% vs. 14%, p=.006), ASXL1 (29% vs. 9%, p=.0005), BCOR (28% vs. 8%, p=.0004), and cohesion mutations (26%, vs. 5%, p=.0005), while NPM1 mutations showed the reverse relationship (1% vs. 7%, p=.03). RAS and CUX1 mutations were mutually exclusive (0% vs. 6%, p=.03). When we analyzed clonal hierarchy in the context of CUX1 mutations; dominant CUX1 mutations (24%; mean VAF=49%); were accomplished by ASXL1 (21%) and SRSF2 (14%) mutations which were the most common secondary events in this context. Phenotypically, dominant CUX1 mutations were associated with MDS/MPN (42%) and MDS (33%). 14% of CUX1 mutant cases did not harbor any other alterations and were not associated with a discernable phenotype. Secondary CUX1 lesions (62%; mean VAF=22%) were found in the context of dominant TET2 mutations (16%). The pathomorphologic context of secondary CUX1 mutation did not differ from that of primary lesions. AML seemed to be underrepresented (p=.006) and MPN overrepresented (p=.019) among dominant CUX1 mutant cases. In conclusion, CUX1 lesions including locus deletions with haploinsuffciency, mutations and a fraction of cases with decreased CUX1 expression can be encountered in MDS and related neoplasms, chiefly AML. CUX1 dysfunction is associated with poor survival likely due to its distinct molecular background. Disclosures Makishima: The Yasuda Medical Foundation: Research Funding. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees

MOESM3 of Biotransformation of ferulic acid to protocatechuic acid by Corynebacterium glutamicum ATCC 21420 engineered to express vanillate O-demethylase

Additional file 3: Figure S2. Growth of C. glutamicum strains F and W in BT-PCA medium. C. glutamicum strains F (closed symbols) and W (open symbols) were grown in 5 mL of BHI medium for 24 h at 30℃. Each starter culture (0.1 mL) was inoculated into 5 mL of BT-2mM PCA medium. The two strains were cultured at 30℃ with agitation at 60 rpm for 24 h. The optical densities at 660nm were monitored once hourly. The data represent the mean and standard error of three independent experiments