Role of T cell-glial cell interactions in creating and amplifying central nervous system inflammation and multiple sclerosis disease symptoms

Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System (CNS) that causes the demyelination of nerve cells and destroys oligodendrocytes, neurons and axons. Historically, MS has been thought of as a T cell-mediated autoimmune disease of CNS white matter. However, recent studies have identified gray matter lesions in MS patients, suggesting that CNS antigens other than myelin proteins may be involved during the MS disease process. We have recently found that T cells targeting astrocyte-specific antigens can drive unique aspects of inflammatory CNS autoimmunity, including the targeting of gray matter and white matter of the brain and inducing heterogeneous clinical disease courses. In addition to being a target of T cells, astrocytes play a critical role in propagating the inflammatory response within the CNS induced NF-kappaB signaling. Here, we will discuss the pathophysiology of CNS inflammation mediated by T cell-glial cell interactions and its contributions to CNS autoimmunity

Polarimetry and the High-Energy Emission Mechanisms in Quasar Jets. The Case of PKS 1136-135

Since the discovery of kiloparsec-scale X-ray emission from quasar jets, the physical processes responsible for their high-energy emission have been poorly defined. A number of mechanisms are under active debate, including synchrotron radiation, inverse-Comptonized CMB (IC/CMB) emission, and other Comptonization processes. In a number of cases, the optical and X-ray emission of jet regions are inked by a single spectral component, and in those, high- resolution multi-band imaging and polarimetry can be combined to yield a powerful diagnostic of jet emission processes. Here we report on deep imaging photometry of the jet of PKS 1136$-$135 obtained with the {\it Hubble Space Telescope.} We find that several knots are highly polarized in the optical, with fractional polarization $\Pi>30$. When combined with the broadband spectral shape observed in these regions, this is very difficult to explain via IC/CMB models, unless the scattering particles are at the lowest-energy tip of the electron energy distribution, with Lorentz factor $\gamma \sim 1$, and the jet is also very highly beamed ($\delta \geq 20$) and viewed within a few degrees of the line of sight. We discuss both the IC/CMB and synchrotron interpretation of the X-ray emission in the light of this new evidence, presenting new models of the spectral energy distribution and also the matter content of this jet. The high polarizations do not completely rule out the possibility of IC/CMB optical-to-X-ray emission in this jet, but they do strongly disfavor the model. We discuss the implications of this finding, and also the prospects for future work.Comment: 14 pages, 8 figures, ApJ in pres

Measuring the Broad-band X-Ray Spectrum from 400 eV to 40 keV in the Southwest Part of the Supernova Remnant RX J1713.7-3946

We report on results from Suzaku broadband X-ray observations of the southwest part of the Galactic supernova remnant (SNR) RX J1713.7-3946 with an energy coverage of 0.4-40 keV. The X-ray spectrum, presumably of synchrotron origin, is known to be completely lineless, making this SNR ideally suited for a detailed study of the X-ray spectral shape formed through efficient particle acceleration at high speed shocks. With a sensitive hard X-ray measurement from the HXD PIN on board Suzaku, we determine the hard X-ray spectrum in the 12--40 keV range to be described by a power law with photon index Gamma = 3.2+/- 0.2, significantly steeper than the soft X-ray index of Gamma = 2.4+/- 0.05 measured previously with ASCA and other missions. We find that a simple power law fails to describe the full spectral range of 0.4-40 keV and instead a power-law with an exponential cutoff with hard index Gamma = 1.50+/- 0.09 and high-energy cutoff epsilon_c = 1.2+/- 0.3 keV formally provides an excellent fit over the full bandpass. If we use the so-called SRCUT model, as an alternative model, it gives the best-fit rolloff energy of epsilon_{roll} = 0.95+/- 0.04 keV. Together with the TeV gamma-ray spectrum ranging from 0.3 to 100 TeV obtained recently by HESS observations, our Suzaku observations of RX J1713.7-3946 provide stringent constraints on the highest energy particles accelerated in a supernova shock.Comment: 11 pages, 11 figures, accepted for publication in Publications of the Astronomical Society of Japan (PASJ

Anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating factor: a case report

<p>Abstract</p> <p>Introduction</p> <p>The granulocyte-colony stimulating factor-producing tumor was first reported in 1977, however, anaplastic pleomorphic type carcinoma of the pancreas producing granulocyte-colony stimulating factor is still rare.</p> <p>Case presentation</p> <p>A 63-year-old man was admitted to our hospital with body weight loss (-10 kg during months) and upper abdominal pain from 3 weeks. Abdominal computed tomography demonstrated a pancreatic tumor 10 cm in size and multiple low-density areas in the liver. On admission, the peripheral leukocyte count was elevated to 91,500/mm³and the serum concentration of granulocyte-colony stimulating factor was 134 pg/mL (normal, < 18.1 pg/mL). Based on liver biopsy findings, the tumor was classified as an anaplastic pleomorphic-type carcinoma. Immunohistochemical staining showed that pancreatic carcinoma cells were positive for granulocyte-colony stimulating factor. The patient developed interstitial pneumonia, probably caused by granulocyte-colony stimulating factor, and died 11 days after admission.</p> <p>Conclusion</p> <p>This is a rare case report of anaplastic pleomorphic-type carcinoma of the pancreas producing granulocyte-colony stimulating factor and confirmed by immunohistochemistry.</p

Suzaku wide-band observations of SN 1006

We report on the wide band spectra of SN 1006 as observed by Suzaku. Thermal and nonthermal emission are successfully resolved thanks to the excellent spectral response of Suzaku's X-ray CCD XIS. The nonthermal emission cannot be reproduced by a simple power-law model but needs a roll-off at 5.7$\times 10^{16}$ Hz = 0.23 keV. The roll-off frequency is significantly higher in the northeastern rim than in the southwestern rim. We also have placed the most stringent upper limit of the flux above 10 keV using the Hard X-ray Detector.Comment: 16 pages, 8 figures, PASJ, in pres

Independent optical excitation of distinct neural populations

Optogenetic tools enable examination of how specific cell types contribute to brain circuit functions. A long-standing question is whether it is possible to independently activate two distinct neural populations in mammalian brain tissue. Such a capability would enable the study of how different synapses or pathways interact to encode information in the brain. Here we describe two channelrhodopsins, Chronos and Chrimson, discovered through sequencing and physiological characterization of opsins from over 100 species of alga. Chrimson's excitation spectrum is red shifted by 45 nm relative to previous channelrhodopsins and can enable experiments in which red light is preferred. We show minimal visual system–mediated behavioral interference when using Chrimson in neurobehavioral studies in Drosophila melanogaster. Chronos has faster kinetics than previous channelrhodopsins yet is effectively more light sensitive. Together these two reagents enable two-color activation of neural spiking and downstream synaptic transmission in independent neural populations without detectable cross-talk in mouse brain slice.PostprintPeer reviewe

Early effects of oral administration of lafutidine with mosapride compared with lafutidine alone on intragastric pH values

<p>Abstract</p> <p>Background</p> <p>The ideal medication for treatment of acid related diseases should have a rapid onset of action to promote hemostasis and resolution of symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after a single oral administrations of lafutidine, is a newly synthesized H2-receptor antagonist, with mosapride 5 mg or lafutidine alone.</p> <p>Methods</p> <p>Ten <it>Helicobacter pylori </it>negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 4 hours after a single oral administration of lafutidine 10 mg or lafutidine 10 mg with mosapride 5 mg (the lafutidine being administrated one hour after the mosapride). Each administration was separated by a 7-day washout period.</p> <p>Results</p> <p>The average pH during the 4-hour period after administration of lafutidine 10 mg with mosapride 5 mg was higher than after lafutidine 10 mg alone (median: 5.25 versus 4.58, respectively; <it>p </it>= 0.0318). During the 3–4 hour study period, lafutidine 10 mg with mosapride 5 mg provided a higher pH, compared to lafutidine 10 mg alone (median: 7.28 versus 6.42; <it>p </it>= 0.0208).</p> <p>Conclusion</p> <p>In <it>H. pylori </it>negative healthy male subjects, an oral dose of lafutidine 10 mg with mosapride 5 mg more rapidly increased intragastric pH than lafutidine 10 mg alone.</p