174 research outputs found
Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease
We present the first application of the hypothesis-rich mathematical theory
to genome-wide association data. The Hamza et al. late-onset sporadic
Parkinson's disease genome-wide association study dataset was analyzed. We
found a rare, coding, non-synonymous SNP variant in the gene DZIP1 that confers
increased susceptibility to Parkinson's disease. The association of DZIP1 with
Parkinson's disease is consistent with a Parkinson's disease stem-cell ageing
theory.Comment: 14 page
Volumetric Magnetic Resonance Imaging Quantification of Longitudinal Brain Changes in Abstinent Alcoholics
Magnetic resonance imaging (MRI) of the brain was performed on a group of 24 recently detoxified, male alcoholics approximately 1 month after their date of last drink. The imaging was repeated 3 months later, at which point 9 subjects had resumed drinking and 15 had maintained abstinence. Contrasts between these two drinking groups revealed that, despite comparable baseline values, the Abstainers exhibited volumetric white matter increases and cerebrospinal fluid reductions over the follow-up interval, whereas the Drinkers did not show significant change on either of these MRI indices. These results provide the first evidence suggestive of significant volumetric white matter increase with abstinence
Search for gamma-ray emission from magnetars with the Fermi Large Area Telescope
We report on the search for 0.1-10 GeV emission from magnetars in 17 months
of Fermi Large Area Telescope (LAT) observations. No significant evidence for
gamma-ray emission from any of the currently-known magnetars is found. The most
stringent upper limits to date on their persistent emission in the Fermi-LAT
energy range are estimated between ~10^{-12}-10^{-10} erg/s/cm2, depending on
the source. We also searched for gamma-ray pulsations and possible outbursts,
also with no significant detection. The upper limits derived support the
presence of a cut-off at an energy below a few MeV in the persistent emission
of magnetars. They also show the likely need for a revision of current models
of outer gap emission from strongly magnetized pulsars, which, in some
realizations, predict detectable GeV emission from magnetars at flux levels
exceeding the upper limits identified here using the Fermi-LAT observations.Comment: ApJ Letters in press; Corresponding authors: Caliandro G. A., Hadasch
D., Rea N., Burnett
Detection of Gamma-Ray Emission from the Starburst Galaxies M82 and NGC 253 with the Large Area Telescope on Fermi
We report the detection of high-energy gamma-ray emission from two starburst
galaxies using data obtained with the Large Area Telescope on board the Fermi
Gamma-ray Space Telescope. Steady point-like emission above 200 MeV has been
detected at significance levels of 6.8 sigma and 4.8 sigma respectively, from
sources positionally coincident with locations of the starburst galaxies M82
and NGC 253. The total fluxes of the sources are consistent with gamma-ray
emission originating from the interaction of cosmic rays with local
interstellar gas and radiation fields and constitute evidence for a link
between massive star formation and gamma-ray emission in star-forming galaxies.Comment: Submitted to ApJ Letter
Fermi Gamma-ray Imaging of a Radio Galaxy
The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating
from the giant radio lobes of the radio galaxy Centaurus A. The resolved
gamma-ray image shows the lobes clearly separated from the central active
source. In contrast to all other active galaxies detected so far in high-energy
gamma-rays, the lobe flux constitutes a considerable portion (>1/2) of the
total source emission. The gamma-ray emission from the lobes is interpreted as
inverse Compton scattered relic radiation from the cosmic microwave background
(CMB), with additional contribution at higher energies from the
infrared-to-optical extragalactic background light (EBL). These measurements
provide gamma-ray constraints on the magnetic field and particle energy content
in radio galaxy lobes, and a promising method to probe the cosmic relic photon
fields.Comment: 27 pages, includes Supplementary Online Material; corresponding
authors: C.C. Cheung, Y. Fukazawa, J. Knodlseder, L. Stawar
Fermi Large Area Telescope observations of PSR J1836+5925
The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly
unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments
of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic
plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8
million years, a spindown luminosity of 1.1 erg s, and a
large off-peak emission component, making it quite unusual among the known
gamma-ray pulsar population. We present an analysis of one year of LAT data,
including an updated timing solution, detailed spectral results and a long-term
light curve showing no indication of variability. No evidence for a surrounding
pulsar wind nebula is seen and the spectral characteristics of the off-peak
emission indicate it is likely magnetospheric. Analysis of recent XMM
observations of the X-ray counterpart yields a detailed characterization of its
spectrum, which, like Geminga, is consistent with that of a neutron star
showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa
A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279
It is widely accepted that strong and variable radiation detected over all
accessible energy bands in a number of active galaxies arises from a
relativistic, Doppler-boosted jet pointing close to our line of sight. The size
of the emitting zone and the location of this region relative to the central
supermassive black hole are, however, poorly known, with estimates ranging from
light-hours to a light-year or more. Here we report the coincidence of a
gamma-ray flare with a dramatic change of optical polarization angle. This
provides evidence for co-spatiality of optical and gamma-ray emission regions
and indicates a highly ordered jet magnetic field. The results also require a
non-axisymmetric structure of the emission zone, implying a curved trajectory
for the emitting material within the jet, with the dissipation region located
at a considerable distance from the black hole, at about 10^5 gravitational
radii.Comment: Published in Nature issued on 18 February 2010. Corresponding
authors: Masaaki Hayashida and Greg Madejsk
Metformin Prevents Nigrostriatal Dopamine Degeneration Independent of AMPK Activation in Dopamine Neurons
Metformin is a widely prescribed drug used to treat type-2 diabetes, although recent studies show it has wide ranging effects to treat other diseases. Animal and retrospective human studies indicate that Metformin treatment is neuroprotective in Parkinson’s Disease (PD), although the neuroprotective mechanism is unknown, numerous studies suggest the beneficial effects on glucose homeostasis may be through AMPK activation. In this study we tested whether or not AMPK activation in dopamine neurons was required for the neuroprotective effects of Metformin in PD. We generated transgenic mice in which AMPK activity in dopamine neurons was ablated by removing AMPK beta 1 and beta 2 subunits from dopamine transporter expressing neurons. These AMPK WT and KO mice were then chronically exposed to Metformin in the drinking water then exposed to MPTP, the mouse model of PD. Chronic Metformin treatment significantly attenuated the MPTP-induced loss of Tyrosine Hydroxylase (TH) neuronal number and volume and TH protein concentration in the nigrostriatal pathway. Additionally, Metformin treatment prevented the MPTP-induced elevation of the DOPAC:DA ratio regardless of genotype. Metformin also prevented MPTP induced gliosis in the Substantia Nigra. These neuroprotective actions were independent of genotype and occurred in both AMPK WT and AMPK KO mice. Overall, our studies suggest that Metformin’s neuroprotective effects are not due to AMPK activation in dopaminergic neurons and that more research is required to determine how metformin acts to restrict the development of PD
Innovation and growth in the UK pharmaceuticals: the case of product and marketing introductions
New drug introductions are key to growth for pharmaceutical firms. However, not all innovations are the same and they may have differential effects that vary by firm size. We use quarterly sales data on UK pharmaceuticals in a dynamic panel model to estimate the impact of product (new drugs) and marketing (additional pack varieties) innovations within a therapeutic class on a firm’s business unit growth. We find that product innovations lead to substantial growth in both the short and long run, whereas a new pack variety only produces short-term effects. The strategies are substitutes but the marginal effects are larger for product innovations relative to additional packs, and the effects are larger for smaller business units. Nonetheless, pack introductions offer a viable short-term growth strategy, especially for small- and medium-sized businesses
Disease-Toxicant Interactions in Manganese Exposed Huntington Disease Mice: Early Changes in Striatal Neuron Morphology and Dopamine Metabolism
YAC128 Huntington's disease (HD) transgenic mice accumulate less manganese (Mn) in the striatum relative to wild-type (WT) littermates. We hypothesized that Mn and mutant Huntingtin (HTT) would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl2-4H2O (50 mg/kg) on days 0, 3 and 6. Striatal medium spiny neuron (MSN) morphology, as well as levels of dopamine (DA) and its metabolites (which are known to be sensitive to Mn-exposure), were analyzed at 13 weeks (7 days from initial exposure) and 16 weeks (28 days from initial exposure). No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age-dependent increase in dendritic length and branching complexity. In addition, genotype-exposure interaction effects were observed for dendritic complexity measures as a function of distance from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore, striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at 16 weeks, both Mn exposure and the HD genotype were associated with quantitatively similar reductions in DA and its metabolites. Interestingly, Mn exposure of YAC128 mice did not further decrease DA or its metabolites versus YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results demonstrate Mn-HD disease-toxicant interactions at the onset of striatal dendritic neuropathology in YAC128 mice. Our results identify the earliest pathological change in striatum of YAC128 mice as being between 13 to 16 weeks. Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as decreased DA levels, while it exacerbates others, such as dendritic pathology
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