68 research outputs found
Gamma-Ray Background from Structure Formation in the Intergalactic Medium
The universe is filled with a diffuse and isotropic extragalactic background
of gamma-ray radiation, containing roughly equal energy flux per decade in
photon energy between 3 MeV-100 GeV. The origin of this background is one of
the unsolved puzzles in cosmology. Less than a quarter of the gamma-ray flux
can be attributed to unresolved discrete sources, but the remainder appears to
constitute a truly diffuse background whose origin has hitherto been
mysterious. Here we show that the shock waves induced by gravity during the
formation of large-scale structure in the intergalactic medium, produce a
population of highly-relativistic electrons with a maximum Lorentz factor above
10^7. These electrons scatter a small fraction of the microwave background
photons in the present-day universe up to gamma-ray energies, thereby providing
the gamma-ray background. The predicted diffuse flux agrees with the observed
background over more than four decades in photon energy, and implies a mean
cosmological density of baryons which is consistent with Big-Bang
nucleosynthesis.Comment: 7 pages, 1 figure. Accepted for publication in Nature. (Press embargo
until published.
Discovery of extreme particle acceleration in the microquasar Cygnus X-3
The study of relativistic particle acceleration is a major topic of
high-energy astrophysics. It is well known that massive black holes in active
galaxies can release a substantial fraction of their accretion power into
energetic particles, producing gamma-rays and relativistic jets. Galactic
microquasars (hosting a compact star of 1-10 solar masses which accretes matter
from a binary companion) also produce relativistic jets. However, no direct
evidence of particle acceleration above GeV energies has ever been obtained in
microquasar ejections, leaving open the issue of the occurrence and timing of
extreme matter energization during jet formation. Here we report the detection
of transient gamma-ray emission above 100 MeV from the microquasar Cygnus X-3,
an exceptional X-ray binary which sporadically produces powerful radio jets.
Four gamma-ray flares (each lasting 1-2 days) were detected by the AGILE
satellite simultaneously with special spectral states of Cygnus X-3 during the
period mid-2007/mid-2009. Our observations show that very efficient particle
acceleration and gamma-ray propagation out of the inner disk of a microquasar
usually occur a few days before major relativistic jet ejections. Flaring
particle energies can be thousands of times larger than previously detected
maximum values (with Lorentz factors of 105 and 102 for electrons and protons,
respectively). We show that the transitional nature of gamma-ray flares and
particle acceleration above GeV energies in Cygnus X-3 is clearly linked to
special radio/X-ray states preceding strong radio flares. Thus gamma-rays
provide unique insight into the nature of physical processes in microquasars.Comment: 29 pages (including Supplementary Information), 8 figures, 2 tables
version submitted to Nature on August 7, 2009 (accepted version available at
http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature08578.pdf
Human first-trimester chorionic villi have a myogenic potential
First-trimester chorionic-villi-derived cells (FTCVs) are the earliest fetal material that can be obtained for prenatal diagnosis of fetal disorders such as Duchenne muscular dystrophy (DMD). DMD is a devastating X-linked disorder characterized by the absence of dystrophin at the sarcolemma of muscle fibers. Currently, a limited number of treatment options are available for DMD, although cell therapy is a promising treatment strategy for muscle degeneration in DMD patients. A novel candidate source of cells for this approach is FTCVs taken between the 9th and 11th weeks of gestation. FTCVs might have a higher undifferentiated potential than any other tissue-derived cells because they are the earliest fetal material. We examined the expression of mesenchymal stem cell and pluripotent stem cell markers in FTCVs, in addition to their myogenic potential. FTCVs expressed mesenchymal stem cell markers and Nanog and Sox2 transcription factors as pluripotent stem cell markers. These cells efficiently differentiated into myotubes after myogenic induction, at which point Nanog and Sox2 were down-regulated, whereas MyoD, myogenin, desmin and dystrophin were up-regulated. To our knowledge, this is the first demonstration that FTCVs can be efficiently directed to differentiate in vitro into skeletal muscle cells that express dystrophin as the last stage marker of myogenic differentiation. The myogenic potential of FTCVs reveals their promise for use in cell therapy for DMD, for which no effective treatment presently exists
Clonal Characterization of Rat Muscle Satellite Cells: Proliferation, Metabolism and Differentiation Define an Intrinsic Heterogeneity
Satellite cells (SCs) represent a distinct lineage of myogenic progenitors responsible for the postnatal growth, repair and maintenance of skeletal muscle. Distinguished on the basis of their unique position in mature skeletal muscle, SCs were considered unipotent stem cells with the ability of generating a unique specialized phenotype. Subsequently, it was demonstrated in mice that opposite differentiation towards osteogenic and adipogenic pathways was also possible. Even though the pool of SCs is accepted as the major, and possibly the only, source of myonuclei in postnatal muscle, it is likely that SCs are not all multipotent stem cells and evidences for diversities within the myogenic compartment have been described both in vitro and in vivo. Here, by isolating single fibers from rat flexor digitorum brevis (FDB) muscle we were able to identify and clonally characterize two main subpopulations of SCs: the low proliferative clones (LPC) present in major proportion (∼75%) and the high proliferative clones (HPC), present instead in minor amount (∼25%). LPC spontaneously generate myotubes whilst HPC differentiate into adipocytes even though they may skip the adipogenic program if co-cultured with LPC. LPC and HPC differ also for mitochondrial membrane potential (ΔΨm), ATP balance and Reactive Oxygen Species (ROS) generation underlying diversities in metabolism that precede differentiation. Notably, SCs heterogeneity is retained in vivo. SCs may therefore be comprised of two distinct, though not irreversibly committed, populations of cells distinguishable for prominent differences in basal biological features such as proliferation, metabolism and differentiation. By these means, novel insights on SCs heterogeneity are provided and evidences for biological readouts potentially relevant for diagnostic purposes described
mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression.
Schwann cell development is hallmarked by the induction of a lipogenic profile. Here we used amniotic fluid stem (AFS) cells and focused on the mechanisms occurring during early steps of differentiation along the Schwann cell lineage. Therefore, we initiated Schwann cell differentiation in AFS cells and monitored as well as modulated the activity of the mechanistic target of rapamycin (mTOR) pathway, the major regulator of anabolic processes. Our results show that mTOR complex 1 (mTORC1) activity is essential for glial marker expression and expression of Sterol Regulatory Element-Binding Protein (SREBP) target genes. Moreover, SREBP target gene activation by statin treatment promoted lipogenic gene expression, induced mTORC1 activation and stimulated Schwann cell differentiation. To investigate mTORC1 downstream signaling we expressed a mutant S6K1, which subsequently induced the expression of the Schwann cell marker S100b, but did not affect lipogenic gene expression. This suggests that S6K1 dependent and independent pathways downstream of mTORC1 drive AFS cells to early Schwann cell differentiation and lipogenic gene expression. In conclusion our results propose that future strategies for peripheral nervous system regeneration will depend on ways to efficiently induce the mTORC1 pathway
The LARGE Principle of Cellular Reprogramming: Lost, Acquired and Retained Gene Expression in Foreskin and Amniotic Fluid-Derived Human iPS Cells
Human amniotic fluid cells (AFCs) are routinely obtained for prenatal diagnostics procedures. Recently, it has been illustrated that these cells may also serve as a valuable model system to study developmental processes and for application in regenerative therapies. Cellular reprogramming is a means of assigning greater value to primary AFCs by inducing self-renewal and pluripotency and, thus, bypassing senescence. Here, we report the generation and characterization of human amniotic fluid-derived induced pluripotent stem cells (AFiPSCs) and demonstrate their ability to differentiate into the trophoblast lineage after stimulation with BMP2/BMP4. We further carried out comparative transcriptome analyses of primary human AFCs, AFiPSCs, fibroblast-derived iPSCs (FiPSCs) and embryonic stem cells (ESCs). This revealed that the expression of key senescence-associated genes are down-regulated upon the induction of pluripotency in primary AFCs (AFiPSCs). By defining distinct and overlapping gene expression patterns and deriving the LARGE (Lost, Acquired and Retained Gene Expression) Principle of Cellular Reprogramming, we could further highlight that AFiPSCs, FiPSCs and ESCs share a core self-renewal gene regulatory network driven by OCT4, SOX2 and NANOG. Nevertheless, these cell types are marked by distinct gene expression signatures. For example, expression of the transcription factors, SIX6, EGR2, PKNOX2, HOXD4, HOXD10, DLX5 and RAXL1, known to regulate developmental processes, are retained in AFiPSCs and FiPSCs. Surprisingly, expression of the self-renewal-associated gene PRDM14 or the developmental processes-regulating genes WNT3A and GSC are restricted to ESCs. Implications of this, with respect to the stability of the undifferentiated state and long-term differentiation potential of iPSCs, warrant further studies
Risk factors in the development of stem cell therapy
Stem cell therapy holds the promise to treat degenerative diseases, cancer and repair of damaged tissues for which there are currently no or limited therapeutic options. The potential of stem cell therapies has long been recognised and the creation of induced pluripotent stem cells (iPSC) has boosted the stem cell field leading to increasing development and scientific knowledge. Despite the clinical potential of stem cell based medicinal products there are also potential and unanticipated risks. These risks deserve a thorough discussion within the perspective of current scientific knowledge and experience. Evaluation of potential risks should be a prerequisite step before clinical use of stem cell based medicinal products
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