Pan-embryo cell dynamics of germlayer formation in zebrafish

Cell movements are coordinated across spatio-temporal scales to achieve precise positioning of organs during vertebrate gastrulation. In zebrafish, mechanisms governing such morphogenetic movements have so far only been studied within a local region or a single germlayer. Here, we present pan-embryo analyses of fate specification and dynamics of all three germlayers simultaneously within a gastrulating embryo, showing that cell movement characteristics are predominantly determined by its position within the embryo, independent of its germlayer identity. The spatially confined fate specification establishes a distinct distribution of cells in each germlayer during early gastrulation. The differences in the initial distribution are subsequently amplified by a unique global movement, which organizes the organ precursors along the embryonic body axis, giving rise to the blueprint of organ formation

INTEGRAL discovery of non-thermal hard X-ray emission from the Ophiuchus cluster

We present the results of deep observations of the Ophiuchus cluster of galaxies with INTEGRAL in the 3-80 keV band. We analyse 3 Ms of INTEGRAL data on the Ophiuchus cluster with the IBIS/ISGRI hard X-ray imager and the JEM-X X-ray monitor. In the X-ray band using JEM-X, we show that the source is extended, and that the morphology is compatible with the results found by previous missions. Above 20 keV, we show that the size of the source is slightly larger than the PSF of the instrument, and is consistent with the soft X-ray morphology found with JEM-X and ASCA. Thanks to the constraints on the temperature provided by JEM-X, we show that the spectrum of the cluster is not well fitted by a single-temperature thermal Bremsstrahlung model, and that another spectral component is needed to explain the high energy data. We detect the high energy tail with a higher detection significance (6.4 sigma) than the BeppoSAX claim (2 sigma). Because of the imaging capabilities of JEM-X and ISGRI, we are able to exclude the possibility that the excess emission comes from very hot regions or absorbed AGN, which proves that the excess emission is indeed of non-thermal origin. Using the available radio data together with the non-thermal hard X-ray flux, we estimate a magnetic field B ~ 0.1-0.2 mu G.Comment: 8 pages, 9 figures, accepted by A&

The Coma cluster magnetic field from Faraday rotation measures

The aim of the present work is to constrain the Coma cluster magnetic field strength, its radial profile and power spectrum by comparing Faraday Rotation Measure (RM) images with numerical simulations of the magnetic field. We have analyzed polarization data for seven radio sources in the Coma cluster field observed with the Very Large Array at 3.6, 6 and 20 cm, and derived Faraday Rotation Measures with kiloparsec scale resolution. Random three dimensional magnetic field models have been simulated for various values of the central intensity B_0 and radial power-law slope eta, where eta indicates how the field scales with respect to the gas density profile. We derive the central magnetic field strength, and radial profile values that best reproduce the RM observations. We find that the magnetic field power spectrum is well represented by a Kolmogorov power spectrum with minimum scale ~ 2 kpc and maximum scale ~ 34 kpc. The central magnetic field strength and radial slope are constrained to be in the range (B_0=3.9 microG; eta=0.4) and (B_0=5.4 microG; eta=0.7) within 1sigma. The best agreement between observations and simulations is achieved for B_0=4.7 microG; eta=0.5. Values of B_0>7 microG and 1.0 are incompatible with RM data at 99 % confidence level.Comment: 23 pages, 21 figures. Higher resolution available at http://www.ira.inaf.it/~bonafede/paper.pdf. A&A accepte

GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology

Friedreich ataxia (FRDA) is a neurodegenerative disorder caused by an unstable GAA repeat expansion mutation within intron 1 of the FXN gene. However, the origins of the GAA repeat expansion, its unstable dynamics within different cells and tissues, and its effects on frataxin expression are not yet completely understood. Therefore, we have chosen to generate representative FRDA mouse models by using the human FXN GAA repeat expansion itself as the genetically modified mutation. We have previously reported the establishment of two lines of human FXN YAC transgenic mice that contain unstable GAA repeat expansions within the appropriate genomic context. We now describe the generation of FRDA mouse models by crossbreeding of both lines of human FXN YAC transgenic mice with heterozygous Fxn knockout mice. The resultant FRDA mice that express only human-derived frataxin show comparatively reduced levels of frataxin mRNA and protein expression, decreased aconitase activity, and oxidative stress, leading to progressive neurodegenerative and cardiac pathological phenotypes. Coordination deficits are present, as measured by accelerating rotarod analysis, together with a progressive decrease in locomotor activity and increase in weight. Large vacuoles are detected within neurons of the dorsal root ganglia (DRG), predominantly within the lumbar regions in 6-month-old mice, but spreading to the cervical regions after 1 year of age. Secondary demyelination of large axons is also detected within the lumbar roots of older mice. Lipofuscin deposition is increased in both DRG neurons and cardiomyocytes, and iron deposition is detected in cardiomyocytes after 1 year of age. These mice represent the first GAA repeat expansion-based FRDA mouse models that exhibit progressive FRDA-like pathology and thus will be of use in testing potential therapeutic strategies, particularly GAA repeat-based strategies. © 2006 Elsevier Inc. All rights reserved

Constraining the population of cosmic ray protons in cooling flow clusters with gamma-ray and radio observations: Are radio mini-halos of hadronic origin?

We wish to constrain the cosmic-ray proton (CRp) population in galaxy clusters. By hadronic interactions with the thermal gas of the intra-cluster medium (ICM), the CRp produce gamma-rays for which we develop an analytic formalism to deduce their spectral distribution. Assuming the CRp-to-thermal energy density ratio X_CRp and the CRp spectral index to be spatially constant, we derive an analytic relation between the gamma-ray and bolometric X-ray fluxes, F_gamma and F_X. Based on our relation, we compile a sample of suitable clusters which are promising candidates for future detection of gamma-rays resulting from hadronic CRp interactions. Comparing to EGRET upper limits, we constrain the CRp population in the cooling flow clusters Perseus and Virgo to X_CRp < 20%. Assuming a plausible value for the CRp diffusion coefficient kappa, we find the central CRp injection luminosity of M 87 to be limited to 10^43 erg s^-1 kappa/(10^29 cm^2 s^-1). The synchrotron emission from secondary electrons generated in CRp hadronic interactions allows even tighter limits to be placed on the CRp population using radio observations. We obtain excellent agreement between the observed and theoretical radio brightness profiles for Perseus, but not for Coma without a radially increasing CRp-to-thermal energy density profile. Since the CRp and magnetic energy densities necessary to reproduce the observed radio flux are very plausible, we propose synchrotron emission from secondary electrons as an attractive explanation of the radio mini-halos found in cooling flow clusters. This model can be tested with future sensitive gamma-ray observations of the accompanying pi0-decays. We identify Perseus (A 426), Virgo, Ophiuchus, and Coma (A 1656) as the most promising candidate clusters for such observations.Comment: 20 pages, 8 figures. Corrected Figure 3 to match the erratum accepted by A&

Architecture of the fungal nuclear pore inner ring complex

The nuclear pore complex (NPC) constitutes the sole gateway for bidirectional nucleocytoplasmic transport. We present the reconstitution and interdisciplinary analyses of the ~425-kDa inner ring complex (IRC), which forms the central transport channel and diffusion barrier of the NPC, revealing its interaction network and equimolar stoichiometry. The Nsp1•Nup49•Nup57 channel nucleoporin hetero-trimer (CNT) attaches to the IRC solely through the adaptor nucleoporin Nic96. The CNT•Nic96 structure reveals that Nic96 functions as an assembly sensor that recognizes the three dimensional architecture of the CNT, thereby mediating the incorporation of a defined CNT state into the NPC. We propose that the IRC adopts a relatively rigid scaffold that recruits the CNT to primarily form the diffusion barrier of the NPC, rather than enabling channel dilation

Variable Expression of Cre Recombinase Transgenes Precludes Reliable Prediction of Tissue-Specific Gene Disruption by Tail-Biopsy Genotyping

The Cre/loxP-system has become the system of choice for the generation of conditional so-called knockout mouse strains, i.e. the tissue-specific disruption of expression of a certain target gene. We here report the loss of expression of Cre recombinase in a transgenic mouse strain with increasing number of generations. This eventually led to the complete abrogation of gene expression of the inserted Cre cDNA while still being detectable at the genomic level. Conversely, loss of Cre expression caused an incomplete or even complete lack of disruption for the protein under investigation. As Cre expression in the tissue of interest in most cases cannot be addressed in vivo during the course of a study, our findings implicate the possibility that individual tail-biopsy genotypes may not necessarily indicate the presence or absence of gene disruption. This indicates that sustained post hoc analyses in regards to efficacy of disruption for every single study group member may be required

Radio Halos From Simulations And Hadronic Models I: The Coma cluster

We use the results from a constrained, cosmological MHD simulation of the Local Universe to predict the radio halo and the gamma-ray flux from the Coma cluster and compare it to current observations. The simulated magnetic field within the Coma cluster is the result of turbulent amplification of the magnetic field during build-up of the cluster. The magnetic seed field originates from star-burst driven, galactic outflows. The synchrotron emission is calculated assuming a hadronic model. We follow four approaches with different distributions for the cosmic-ray proton (CRp) population within galaxy clusters. The radial profile the radio halo can only be reproduced with a radially increasing energy fraction within the cosmic ray proton population, reaching $>$100% of the thermal energy content at $\approx$ 1Mpc, e.g. the edge of the radio emitting region. Additionally the spectral steepening of the observed radio halo in Coma cannot be reproduced, even when accounting for the negative flux from the thermal SZ effect at high frequencies. Therefore the hadronic models are disfavored from present analysis. The emission of $\gamma$-rays expected from our simulated coma is still below the current observational limits (by a factor of $\sim$6) but would be detectable in the near future.Comment: Submitted to MNRAS, 5pages, 3 figures, 1 tabl

Clusters of galaxies : observational properties of the diffuse radio emission

Clusters of galaxies, as the largest virialized systems in the Universe, are ideal laboratories to study the formation and evolution of cosmic structures...(abridged)... Most of the detailed knowledge of galaxy clusters has been obtained in recent years from the study of ICM through X-ray Astronomy. At the same time, radio observations have proved that the ICM is mixed with non-thermal components, i.e. highly relativistic particles and large-scale magnetic fields, detected through their synchrotron emission. The knowledge of the properties of these non-thermal ICM components has increased significantly, owing to sensitive radio images and to the development of theoretical models. Diffuse synchrotron radio emission in the central and peripheral cluster regions has been found in many clusters. Moreover large-scale magnetic fields appear to be present in all galaxy clusters, as derived from Rotation Measure (RM) studies. Non-thermal components are linked to the cluster X-ray properties, and to the cluster evolutionary stage, and are crucial for a comprehensive physical description of the intracluster medium. They play an important role in the cluster formation and evolution. We review here the observational properties of diffuse non-thermal sources detected in galaxy clusters: halos, relics and mini-halos. We discuss their classification and properties. We report published results up to date and obtain and discuss statistical properties. We present the properties of large-scale magnetic fields in clusters and in even larger structures: filaments connecting galaxy clusters. We summarize the current models of the origin of these cluster components, and outline the improvements that are expected in this area from future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics Review. 58 pages, 26 figure

Lentivirus-meditated frataxin gene delivery reverses genome instability in Friedreich ataxia patient and mouse model fibroblasts

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by deficiency of frataxin protein, with the primary sites of pathology being the large sensory neurons of the dorsal root ganglia and the cerebellum. FRDA is also often accompanied by severe cardiomyopathy and diabetes mellitus. Frataxin is important in mitochondrial iron–sulfur cluster (ISC) biogenesis and low-frataxin expression is due to a GAA repeat expansion in intron 1 of the FXN gene. FRDA cells are genomically unstable, with increased levels of reactive oxygen species and sensitivity to oxidative stress. Here we report the identification of elevated levels of DNA double strand breaks (DSBs) in FRDA patient and YG8sR FRDA mouse model fibroblasts compared to normal fibroblasts. Using lentivirus FXN gene delivery to FRDA patient and YG8sR cells, we obtained long-term overexpression of FXN mRNA and frataxin protein levels with reduced DSB levels towards normal. Furthermore, γ-irradiation of FRDA patient and YG8sR cells revealed impaired DSB repair that was recovered on FXN gene transfer. This suggests that frataxin may be involved in DSB repair, either directly by an unknown mechanism, or indirectly via ISC biogenesis for DNA repair enzymes, which may be essential for the prevention of neurodegeneration.Ataxia UK, FARA Australasia and FARA US