Downstream genes of Pax6 revealed by comprehensive transcriptome profiling in the developing rat hindbrain

Abstract Background The transcription factor Pax6 is essential for the development of the central nervous system and it exerts its multiple functions by regulating the expression of downstream target molecules. To screen for genes downstream of Pax6, we performed comprehensive transcriptome profiling analyses in the early hindbrain of Pax6 homozygous mutant and wild-type rats using microarrays. Results Comparison of quadruplicate microarray experiments using two computational methods allowed us to identify differentially expressed genes that have relatively small fold changes or low expression levels. Gene ontology analyses of the differentially expressed molecules demonstrated that Pax6 is involved in various signal transduction pathways where it regulates the expression of many receptors, signaling molecules, transporters and transcription factors. The up- or down-regulation of these genes was further confirmed by quantitative RT-PCR. In situ staining of Fabp7, Dbx1, Unc5h1 and Cyp26b1 mRNAs showed that expression of these transcripts not only overlapped with that of Pax6 in the hindbrain of wild-type and Pax6 heterozygous mutants, but also was clearly reduced in the hindbrain of the Pax6 homozygous mutant. In addition, the Pax6 homozygous mutant hindbrain showed that Cyp26b1 expression was lacked in the dorsal and ventrolateral regions of rhombomeres 5 and 6, and that the size of rhombomere 5 expanded rostrocaudally. Conclusions These results indicate that Unc5h1 and Cyp26b1 are novel candidates for target genes transactivated by Pax6. Furthermore, our results suggest the interesting possibility that Pax6 regulates anterior-posterior patterning of the hindbrain via activation of Cyp26b1, an enzyme that metabolizes retinoic acid

Suzaku Observation of HCG 62: Temperature, Abundance, and Extended Hard X-ray Emission Profiles

We present results of 120 ks observation of a compact group of galaxies HCG~62 ($z=0.0145$) with Suzaku XIS and HXD-PIN\@. The XIS spectra for four annular regions were fitted with two temperature {\it vapec} model with variable abundance, combined with the foreground Galactic component. The Galactic component was constrained to have a common surface brightness among the four annuli, and two temperature {\it apec} model was preferred to single temperature model. We confirmed the multi-temperature nature of the intra-group medium reported with Chandra and XMM-Newton, with a doughnut-like high temperature ring at radii 3.3--6.5$'$ in a hardness image. We found Mg, Si, S, and Fe abundances to be fairly robust. We examined the possible ``high-abundance arc'' at $\sim 2'$ southwest from the center, however Suzaku data did not confirm it. We suspect that it is a misidentification of an excess hot component in this region as the Fe line. Careful background study showed no positive detection of the extended hard X-rays previously reported with ASCA, in 5--12 keV with XIS and 12--40 keV with HXD-PIN, although our upper limit did not exclude the ASCA result. There is an indication that the X-ray intensity in $r<3.3'$ region is $70\pm 19$% higher than the nominal CXB level (5--12 keV), and Chandra and Suzaku data suggest that most of this excess could be due to concentration of hard X-ray sources with an average photon index of $\Gamma=1.38\pm 0.06$. Cumulative mass of O, Fe and Mg in the group gas and the metal mass-to-light ratio were derived and compared with those in other groups. Possible role of AGN or galaxy mergers in this group is also discussed.Comment: 29 pages with 9 figures, accepted for publication in PASJ Vol 60, second Suzaku special issu

Do Cross-Language Script Differences Enable Bilinguals to Function Selectively When Speaking in One Language Alone?

The present study examined the role of script in bilingual speech planning by comparing the performance of same and different-script bilinguals. Spanish-English bilinguals (Experiment 1) and Japanese-English bilinguals (Experiment 2) performed a picture-word interference task in which they were asked to name a picture of an object in English, their second language, while ignoring a visual distractor word in Spanish or Japanese, their first language. Results replicated the general pattern seen in previous bilingual picture-word interference studies for the same-script, Spanish-English bilinguals but not for the different-script, Japanese-English bilinguals. Both groups showed translation facilitation, whereas only Spanish-English bilinguals demonstrated semantic interference, phonological facilitation, and phono-translation facilitation. These results suggest that when the script of the language not in use is present in the task, bilinguals appear to exploit the perceptual difference as a language cue to direct lexical access to the intended language earlier in the process of speech planning

Switchmate! An Electrophysiological Attempt to Adjudicate Between Competing Accounts of Adjective-Noun Code-Switching.

Here, we used event-related potentials to test the predictions of two prominent accounts of code-switching in bilinguals: The Matrix Language Framework (MLF; Myers-Scotton, 1993) and an application of the Minimalist Programme (MP; Cantone and MacSwan, 2009). We focused on the relative order of the noun with respect to the adjective in mixed Welsh-English nominal constructions given the clear contrast between pre- and post-nominal adjective position between Welsh and English. MP would predict that the language of the adjective should determine felicitous word order (i.e., English adjectives should appear pre-nominally and Welsh adjectives post-nominally). In contrast, MLF contends that it is the language of the finite verb inflexion rather than that of a particular word that governs felicitous word order. To assess the predictions of the two models, we constructed sentences featuring a code-switch between the adjective and the noun, that complied with either English or Welsh word-order. Highly proficient Welsh-English bilinguals made semantic acceptability judgements upon reading the last word of sentences which could violate MP assumptions, MLF assumptions, both assumptions, or neither. Behaviourally, MP violations had no significant effect, whereas MLF violations induced an average drop of 11% in acceptability judgements. Neurophysiologically, MP violations elicited a significant Left Anterior Negativity (LAN) modulation, whereas MLF violations modulated both P600 and LAN mean amplitudes. In addition, there was a significant interaction between MP and MLF status in the P600 range: When MP was violated, MLF status did not matter, and when MP criteria were met, MLF violations resulted in a P600 modulation. This interaction possibly reflects a general preference for noun over adjective insertions, and may provide support for MLF over MP at a global sentence processing level. Model predictions also manifested differently in each of the matrix languages (MLs): When the ML was Welsh, MP and MLF violations elicited greater P600 mean amplitudes than MP and MLF adherences, however, this pattern was not observed when the ML was English. We discuss methodological considerations relating to the neuroscientific study of code-switching, and the extent to which our results shed light on adjective-noun code-switching beyond findings from production and experimental-behavioural studies

Simple generation of hairless mice for in vivo imaging

The in vivo imaging of mice makes it possible to analyze disease progress non-invasively through reporter gene expression. As the removal of hair improves the accuracy of in vivo imaging, gene-modified mice with a reporter gene are often crossed with Hos:HR-1 mutant mice homozygous for the spontaneous Hrhr mutation that exhibit a hair loss phenotype. However, it is time consuming to produce mice carrying both the reporter gene and mutant Hrhr gene by mating. In addition, there is a risk that genetic background of the gene-modified mice would be altered by mating. To resolve these issues, we established a simple method to generate hairless mice maintaining the original genetic background by CRISPR technology. First, we constructed the pX330 vector, which targets exon 3 of Hr. This DNA vector (5 ng/µl) was microinjected into the pronuclei of C57BL/6J mice. Induced Hr gene mutations were found in many founders (76.1%) and these mutations were heritable. Next, we performed in vivo imaging using these gene-modified hairless mice. As expected, luminescent objects in their body were detected by in vivo imaging. This study clearly showed that hairless mice could be simply generated by the CRISPR/Cas9 system, and this method may be useful for in vivo imaging studies with various gene-modified mice

Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.

横紋筋肉腫におけるゲノム・エピゲノム異常の全体図を解明 -横紋筋肉腫を4群に分類-. 京都大学プレスリリース. 2015-07-03.Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS

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

An eight-year follow-up national study of medical school and general hospital ethics committees in Japan

<p>Abstract</p> <p>Background</p> <p>Ethics committees and their system of research protocol peer-review are currently used worldwide. To ensure an international standard for research ethics and safety, however, data is needed on the quality and function of each nation's ethics committees. The purpose of this study was to describe the characteristics and developments of ethics committees established at medical schools and general hospitals in Japan.</p> <p>Methods</p> <p>This study consisted of four national surveys sent twice over a period of eight years to two separate samples. The first target was the ethics committees of all 80 medical schools and the second target was all general hospitals with over 300 beds in Japan (n = 1457 in 1996 and n = 1491 in 2002). Instruments contained four sections: (1) committee structure, (2) frequency of annual meetings, (3) committee function, and (4) existence of a set of guidelines for the refusal of blood transfusion by Jehovah's Witnesses.</p> <p>Results</p> <p>Committee structure was overall interdisciplinary. Frequency of annual meetings increased significantly for both medical school and hospital ethics committees over the eight years. The primary activities for medical school and hospital ethics committees were research protocol reviews and policy making. Results also showed a significant increase in the use of ethical guidelines, particularly those related to the refusal of blood transfusion by Jehovah's Witnesses, among both medical school and hospital ethics committees.</p> <p>Conclusion</p> <p>Overall findings indicated a greater recognized degree of responsibilities and an increase in workload for Japanese ethics committees.</p