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Disrupted CXCR2 Signaling in Oligodendroglia Lineage Cells Enhances Myelin Repair in a Viral Model of Multiple Sclerosis.
CXCR2 is a chemokine receptor expressed on oligodendroglia that has been implicated in the pathogenesis of neuroinflammatory demyelinating diseases as well as enhancement of the migration, proliferation, and myelin production by oligodendroglia. Using an inducible proteolipid protein (Plp) promoter-driven Cre-loxP recombination system, we were able to assess how timed ablation of Cxcr2 in oligodendroglia affected disease following intracranial infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Generation of Plp-Cre-ER(T)::Cxcr2flox/flox transgenic mice (termed Cxcr2-CKO mice) allows for Cxcr2 to be silenced in oligodendrocytes in adult mice following treatment with tamoxifen. Ablation of oligodendroglia Cxcr2 did not influence clinical severity in response to intracranial infection with JHMV. Infiltration of activated T cells or myeloid cells into the central nervous system (CNS) was not affected, nor was the ability to control viral infection. In addition, the severity of demyelination was similar between tamoxifen-treated mice and vehicle-treated controls. Notably, deletion of Cxcr2 resulted in increased remyelination, as assessed by g-ratio (the ratio of the inner axonal diameter to the total outer fiber diameter) calculation, compared to that in vehicle-treated control mice. Collectively, our findings argue that CXCR2 signaling in oligodendroglia is dispensable with regard to contributing to neuroinflammation, but its deletion enhances remyelination in a preclinical model of the human demyelinating disease multiple sclerosis (MS).IMPORTANCE Signaling through the chemokine receptor CXCR2 in oligodendroglia is important for developmental myelination in rodents, while chemical inhibition or nonspecific genetic deletion of CXCR2 appears to augment myelin repair in animal models of the human demyelinating disease multiple sclerosis (MS). To better understand the biology of CXCR2 signaling on oligodendroglia, we generated transgenic mice in which Cxcr2 is selectively ablated in oligodendroglia upon treatment with tamoxifen. Using a viral model of neuroinflammation and demyelination, we demonstrate that genetic silencing of CXCR2 on oligodendroglia did not affect clinical disease, neuroinflammation, or demyelination, yet there was increased remyelination. These findings support and extend previous findings suggesting that targeting CXCR2 may offer a therapeutic avenue for enhancing remyelination in patients with demyelinating diseases
Phytoplankton bloom phenomena in the North Atlantic Ocean and Arabian Sea
Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of International Council for the Exploration of the Sea for personal use, not for redistribution. The definitive version was published in ICES Journal of Marine Science 72 (2015): 2021-2028, doi:10.1093/icesjms/fsu241.We review bio-optical and physical data from three mooring experiments, the Marine Light–Mixed Layers programme in spring 1989 and 1991 in the Iceland Basin (59°N/21°W), and the Forced Upper Ocean Dynamics Experiment in the central Arabian Sea from October 1994 to 1995 (15.5°N/61.5°E). In the Iceland Basin, from mid-April to mid-June in 1989, chlorophyll-a concentrations are sensitive to small changes in stratification, with intermittent increases early in the record. The spring increase occurs after 20 May, coincident with persistent water column stratification. In 1991, the bloom occurs 2 weeks earlier than in 1989, with a background of strong short-term and diurnal variability in mixed layer depth and minimal horizontal advection. In the Arabian Sea, the mixing response to the northeast and southwest monsoons, plus the response to mesoscale eddies, produces four blooms over the annual cycle. The mixed layer depth in the Arabian Sea never exceeds the euphotic zone, allowing interactions between phytoplankton and grazer populations to become important. For all three mooring experiments, change in water column stratification is key in producing phytoplankton blooms.2016-01-0
Autophagy of mucin granules contributes to resolution of airway mucous metaplasia
Abstract Exacerbations of muco-obstructive airway diseases such as COPD and asthma are associated with epithelial changes termed mucous metaplasia (MM). Many molecular pathways triggering MM have been identified; however, the factors that regulate resolution are less well understood. We hypothesized that the autophagy pathway is required for resolution of MM by eliminating excess non-secreted intracellular mucin granules. We found increased intracellular levels of mucins Muc5ac and Muc5b in mice deficient in autophagy regulatory protein, Atg16L1, and that this difference was not due to defects in the known baseline or stimulated mucin secretion pathways. Instead, we found that, in mucous secretory cells, Lc3/Lamp1 vesicles colocalized with mucin granules particularly adjacent to the nucleus, suggesting that some granules were being eliminated in the autophagy pathway rather than secreted. Using a mouse model of MM resolution, we found increased lysosomal proteolytic activity that peaked in the days after mucin production began to decline. In purified lysosomal fractions, Atg16L1-deficient mice had reduced proteolytic degradation of Lc3 and Sqstm1 and persistent accumulation of mucin granules associated with impaired resolution of mucous metaplasia. In normal and COPD derived human airway epithelial cells (AECs), activation of autophagy by mTOR inhibition led to a reduction of intracellular mucin granules in AECs. Our findings indicate that during peak and resolution phases of MM, autophagy activity rather than secretion is required for elimination of some remaining mucin granules. Manipulation of autophagy activation offers a therapeutic target to speed resolution of MM in airway disease exacerbations
Report of the panel on earth rotation and reference frames, section 7
Objectives and requirements for Earth rotation and reference frame studies in the 1990s are discussed. The objectives are to observe and understand interactions of air and water with the rotational dynamics of the Earth, the effects of the Earth's crust and mantle on the dynamics and excitation of Earth rotation variations over time scales of hours to centuries, and the effects of the Earth's core on the rotational dynamics and the excitation of Earth rotation variations over time scales of a year or longer. Another objective is to establish, refine and maintain terrestrial and celestrial reference frames. Requirements include improvements in observations and analysis, improvements in celestial and terrestrial reference frames and reference frame connections, and improved observations of crustal motion and mass redistribution on the Earth
Predictors of failed attendances in a multi-specialty outpatient centre using electronic databases.
BACKGROUND: Failure to keep outpatient medical appointments results in inefficiencies and costs. The objective of this study is to show the factors in an existing electronic database that affect failed appointments and to develop a predictive probability model to increase the effectiveness of interventions. METHODS: A retrospective study was conducted on outpatient clinic attendances at Tan Tock Seng Hospital, Singapore from 2000 to 2004. 22864 patients were randomly sampled for analysis. The outcome measure was failed outpatient appointments according to each patient's latest appointment. RESULTS: Failures comprised of 21% of all appointments and 39% when using the patients' latest appointment. Using odds ratios from the mutliple logistic regression analysis, age group (0.75 to 0.84 for groups above 40 years compared to below 20 years), race (1.48 for Malays, 1.61 for Indians compared to Chinese), days from scheduling to appointment (2.38 for more than 21 days compared to less than 7 days), previous failed appointments (1.79 for more than 60% failures and 4.38 for no previous appointments, compared with less than 20% failures), provision of cell phone number (0.10 for providing numbers compared to otherwise) and distance from hospital (1.14 for more than 14 km compared to less than 6 km) were significantly associated with failed appointments. The predicted probability model's diagnostic accuracy to predict failures is more than 80%. CONCLUSION: A few key variables have shown to adequately account for and predict failed appointments using existing electronic databases. These can be used to develop integrative technological solutions in the outpatient clinic
X-ray spectroscopy and photometry of the long-period polar AI Tri with XMM-Newton
Context. The energy balance of cataclysmic variables with strong magnetic
fields is a central subject in understanding accretion processes on magnetic
white dwarfs. With XMM-Newton, we perform a spectroscopic and photometric study
of soft X-ray selected polars during their high states of accretion. Aims. On
the basis of X-ray and optical observations of the magnetic cataclysmic
variable AI Tri, we derive the properties of the spectral components, their
flux contributions, and the physical structure of the accretion region in soft
polars. Methods. We use multi-temperature approaches in our xspec modeling of
the spectra to describe the physical conditions and the structures of the
post-shock accretion flow and the accretion spot on the white-dwarf surface. In
addition, we investigate the accretion geometry of the system by a timing
analysis of the photometric data. Results. Flaring soft X-ray emission from the
heated surface of the white dwarf dominates the X-ray flux during roughly 70%
of the binary cycle. This component deviates from a single black body and can
be described by a superimposition of mildly absorbed black bodies with a
Gaussian temperature distribution. In addition, weaker hard X-ray emission is
visible nearly all the time. The spectrum from the cooling post-shock accretion
flow is most closely fitted by a combination of thermal plasma mekal models
with temperature profiles adapted from prior stationary two-fluid hydrodynamic
calculations. The soft X-ray light curves show a dip during the bright phase,
which can be interpreted as self-absorption in the accretion stream.
Phase-resolved spectral modeling supports the picture of one-pole accretion and
self-eclipse. One of the optical light curves corresponds to an irregular mode
of accretion. During a short XMM-Newton observation at the same epoch, the
X-ray emission of the system is clearly dominated by the soft component.Comment: A&A, in press; 11 pages, 9 figures, 3 table
The Marine light - mixed layer experiment cruise and data report, R/V Endeavor : cruise EN-224, mooring deployment, 27 April-1 May 1991, cruise EN-227, mooring recovery, 5-23 September 1991
The Marine Light - Mixed Layer experiment took place in the sub-Arctic North Atlantic ocean, approximately 275 miles
south of Reykjavik, Iceland. The field program included a central surface mooring to document the temporal evolution of physical,
biological and optical properties. The surface mooring was deployed at approximately 59°N, 21°W on 29 April 1991 and recovered
on 6 September 1991. The Upper Ocean Processes Group of the Woods Hole Oceanographic Institution was responsible for design,
preparation, deployment, and recovery of the mooring. The Group's contrbution to the field measurements included four different
types of sensors: a meteorological observation package on the surface buoy, a string of 15 temperature sensors along the mooring
line, an acoustic Doppler current profiler, and four instruments for measuring mooring tension and accelerations. The observations
obtained from the mooring are sufficient to describe the air-sea fluxes and the local physical response to surface forcing. The
objective in the analysis phase will be to determine the factors controlling this physical response and to work towards an understanding
of the links among physical, biological, and optical processes. This report describes the deployment and recovery of the
mooring, the meteorological data, and the subsurface temperature and current data.Funding was provided by the Office of Naval Research under Contract N00014-89-J-1683
X-ray variability in a complete sample of Soft X-ray selected AGN
We present ROSAT All-Sky Survey and ROSAT pointed observations (PSPC and HRI)
of a complete sample of 113 bright soft X-ray AGN selected from the ROSAT
Bright Source Catalog. We compare these observations in order to search for
extreme cases of flux and spectral X-ray variability - X-ray transient AGN.
Three definite transients and one transient candidate are found.
The other sources show amplitude variations typically by factors of 2-3 on
timescales of years. We found that the variability strength on timescales of
days is a function of the steepness of the X-ray spectrum: steeper X-ray
objects show stronger variability than flat X-ray spectrum sources. We also
present new HRI measurements of our extreme X-ray transients IC 3599 and
WPVS007. We discuss possible models to explain the X-ray transience and the
variabilities observed in the non-transient sources.Comment: 17 pages (including 7 Figures), accepted for in A&A (main journal),
also available at http://www.xray.mpe.mpg.de/~dgrupe/research/refereed.htm
X-ray observations of three young, early-type galaxies
Massive haloes of hot plasma exist around some, but not all elliptical galaxies. There is evidence that this is related to the age of the galaxy. In this paper, new X-ray observations are presented for three early-type galaxies that show evidence of youth, in order to investigate their X-ray components and properties. NGC 5363 and NGC 2865 were found to have X-ray emission dominated by purely discrete stellar sources. Limits are set on the mass distribution in one of the galaxies observed with XMM–Newton, NGC 4382, which contains significant hot gas. We detect the X-ray emission in NGC 4382 out to 4re. The mass-to-light ratio is consistent with a stellar origin in the inner regions but rises steadily to values indicative of some dark matter by 4re. These results are set in context with other data drawn from the literature, for galaxies with ages estimated from dynamical or spectroscopic indicators. Ages obtained from optical spectroscopy represent central luminosity-weighted stellar ages. We examine the X-ray evolution with age, normalized by B- and K-band luminosities. Low values of Log(LX/LB) and Log(LX/LK) are found for all galaxies with ages between 1 and 4 Gyr. Luminous X-ray emission only appears in older galaxies. This suggests that the interstellar medium is removed and then it takes several gigayears for hot gas haloes to build up, following a merger. A possible mechanism for gas expulsion might be associated with feedback from an active nucleus triggered during a merger
RX J2217.9--5941: A highly X-ray variable Narrow-Line Seyfert1 galaxy
We report the discovery of a highly X-ray variable AGN, RX J2217.9-5941. This
object was bright during the ROSAT All-Sky Survey (RASS), during which a
decrease in the count rate by a factor of 12 was observed. It was found to be
much fainter in follow-up HRI observations and is therefore an X-ray transient
AGN candidate. On long time scales of years, its count rate decreased by a
factor of about 30 between the RASS and the ROSAT HRI and ASCA observations in
1998. Analysis of the ASCA data, complicated by source confusion and poor
statistics, tentatively indicates a steep spectrum in the faint state. There is
no evidence for variability among 5 optical observations of the object obtained
between 1992 and 1998. We discuss the variability of RX J2217.9-5941 and its
possible X-ray transient nature.Comment: 10 pages (including 7 Figures), accepted for A&A, also available at
http://www.xray.mpe.mpg.de/~dgrupe/research/refereed.htm
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