343 research outputs found
Adult hematopoietic progenitors are pluripotent in chimeric mice
18 pages, 7 figures.Embryonic stem cells (ESCs) and adult somatic cells, induced to pluripotency (iPSCs) by genetic manipulation, display high self-Âârenewal potential and the capacity to differentiate into multiple cell lineages. We asked whether there are in adult mammals natural stem cells that are pluripotent. We previously reported that normal adult mammalian bone marrow contains a sub-Ââpopulation of CD34+ cells, that naturally expresses genes characteristic of ESCs and those required to generate iPSCs, but have a limited lifespan and do not form teratomas. In addition, these CD34+ cells spontaneously express, without genetic manipulation, genes characteristic of the three embryonic germ layers: i.e., ectodermal neural, mesodermal cardiac muscle, and endodermal pancreatic and intestinal lineage genes (Pessac, B, et al. 2011. Hematopoietic progenitors express embryonic stem cell and germ layer genes. Comptes Rendus Biologies 334: 300-Ââ306). This suggested that these cells may be pluripotent. Here we have transplanted these CD34+ bone marrow stem cells from adult male C56Bl/6J ROSA mice, that carry two markers: the Ă-Ââgalactosidase gene and the male Y chromosome, into blastocysts of wildtype C57Bl/6J mice. These blastocysts develop normally and give rise to healthy adult chimeric mice. Each female ROSA chimeric mouse had a distinct pattern of male organs expressing Ă-Ââgalactosidase derived from each of the three embryonic germ layers: ectodermal brain, dorsal root ganglia and skin; mesodermal heart, bone and bone marrow; and endodermal pancreas, intestine, and liver. Thus, adult mammals still carry cells that appear to exhibit a developmental potential comparable to ESCs and iPSCs suggesting that CD34+ cells from adult bone marrow could be used for cell therapy
Comparison of urinary 6âÎČâcortisol and the erythromycin breath test as measures of hepatic P450IIIA (CYP3A) activity
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110077/1/cptclpt1992140.pd
The optical counterpart to gamma-ray burst GRB970228 observed using the Hubble Space Telescope
Although more than 2,000 astronomical gamma-ray bursts (GRBs) have been
detected, and numerous models proposed to explain their occurrence, they have
remained enigmatic owing to the lack of an obvious counterpart at other
wavelengths. The recent ground-based detection of a transient source in the
vicinity of GRB 970228 may therefore have provided a breakthrough. The optical
counterpart appears to be embedded in an extended source which, if a galaxy as
has been suggested, would lend weight to those models that place GRBs at
cosmological distances. Here we report the observations using the Hubble Space
Telescope of the transient counterpart and extended source 26 and 39 days after
the initial gamma-ray outburst. We find that the counterpart has faded since
the initial detection (and continues to fade), but the extended source exhibits
no significant change in brightness between the two dates of observations
reported here. The size and apparent constancy between the two epochs of HST
observations imply that it is extragalactic, but its faintness makes a
definitive statement about its nature difficult. Nevertheless, the decay
profile of the transient source is consistent with a popular impulsive-fireball
model, which assumes a merger between two neutron stars in a distant galaxy.Comment: 11 pages + 2 figures. To appear in Nature (29 May 1997 issue
Coherent Manipulation of Quantum Delta-kicked Dynamics: Faster-than-classical Anomalous Diffusion
Large transporting regular islands are found in the classical phase space of
a modified kicked rotor system in which the kicking potential is reversed after
every two kicks. The corresponding quantum system, for a variety of system
parameters and over long time scales, is shown to display energy absorption
that is significantly faster than that associated with the underlying classical
anomalous diffusion. The results are of interest to both areas of quantum chaos
and quantum control.Comment: 6 pages, 4 figures, to appear in Physical Review
Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimerâs disease-relevant murine model
Mitochondrial dysfunction is a hallmark of neurodegenerative diseases including Alzheimerâs disease (AD), with morphological and functional abnormalities limiting the electron transport chain and ATP production. A contributing factor of mitochondrial abnormalities is loss of nicotinamide adenine dinucleotide (NAD), an important cofactor in multiple metabolic reactions. Depletion of mitochondrial and consequently cellular NAD(H) levels by activated NAD glycohydrolases then culminates in bioenergetic failure and cell death. De Novo NAD+ synthesis from tryptophan requires a multi-step enzymatic reaction. Thus, an alternative strategy to maintain cellular NAD+ levels is to administer NAD+ precursors facilitating generation via a salvage pathway. We administered nicotinamide mononucleotide (NMN), an NAD+ precursor to APP(swe)/PS1(ÎE9) double transgenic (AD-Tg) mice to assess amelioration of mitochondrial respiratory deficits. In addition to mitochondrial respiratory function, we examined levels of full-length mutant APP, NAD+-dependent substrates (SIRT1 and CD38) in homogenates and fission/fusion proteins (DRP1, OPA1 and MFN2) in mitochondria isolated from brain. To examine changes in mitochondrial morphology, bigenic mice possessing a fluorescent protein targeted to neuronal mitochondria (CaMK2a-mito/eYFP), were administered NMN. Mitochondrial oxygen consumption rates were examined in N2A neuroblastoma cells and non-synaptic brain mitochondria isolated from mice (3 months). Western blotting was utilized to assess APP, SIRT1, CD38, DRP1, OPA1 and MFN2 in brain of transgenic and non-transgenic mice (3â12 months). Mitochondrial morphology was assessed with confocal microscopy. One-way or two-way analysis of variance (ANOVA) and post-hoc Holm-Sidak method were used for statistical analyses of data. Student t-test was used for direct comparison of two groups. We now demonstrate that mitochondrial respiratory function was restored in NMN-treated AD-Tg mice. Levels of SIRT1 and CD38 change with age and NMN treatment. Furthermore, we found a shift in dynamics from fission to fusion proteins in the NMN-treated mice. This is the first study to directly examine amelioration of NAD+ catabolism and changes in mitochondrial morphological dynamics in brain utilizing the immediate precursor NMN as a potential therapeutic compound. This might lead to well-defined physiologic abnormalities that can serve an important role in the validation of promising agents such as NMN that target NAD+ catabolism preserving mitochondrial function.https://doi.org/10.1186/s12883-015-0272-
Beam test results for the FiberGLAST instrument
The FiberGLAST scintillating fiber telescope is a large-area instrument concept for NASA\u27s GLAST program. The detector is designed for high-energy gamma-ray astronomy, and uses plastic scintillating fibers to combine a photon pair tracking telescope and a calorimeter into a single instrument. A small prototype detector has been tested with high energy photons at the Thomas Jefferson National Accelerator Facility. We report on the result of this beam test, including scintillating fiber performance, photon track reconstruction, angular resolution, and detector efficiency
Control of Dynamical Localization
Control over the quantum dynamics of chaotic kicked rotor systems is
demonstrated. Specifically, control over a number of quantum coherent phenomena
is achieved by a simple modification of the kicking field. These include the
enhancement of the dynamical localization length, the introduction of classical
anomalous diffusion assisted control for systems far from the semiclassical
regime, and the observation of a variety of strongly nonexponential lineshapes
for dynamical localization. The results provide excellent examples of
controlled quantum dynamics in a system that is classically chaotic and offer
new opportunities to explore quantum fluctuations and correlations in quantum
chaos.Comment: 9 pages, 7 figures, to appear in Physical Review
Estimation of GRB detection by FiberGLAST
FiberGLAST is one of several instrument concepts being developed for possible inclusion as the primary Gamma-ray Large Area Space Telescope (GLAST) instrument. The predicted FiberGLAST effective area is more than 12,000 cm2 for energies between 30 MeV and 300 GeV, with a field of view that is essentially flat from 0°â80°. The detector will achieve a sensitivity more than 10 times that of EGRET. We present results of simulations that illustrate the sensitivity of FiberGLAST for the detection of gamma-ray bursts
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