Production of IL-16 correlates with CD4+ Th1 inflammation and phosphorylation of axonal cytoskeleton in multiple sclerosis lesions

BACKGROUND: Multiple sclerosis (MS) is a central nervous system-specific autoimmune, demyelinating and neurodegenerative disease. Infiltration of lesions by autoaggressive, myelin-specific CD4+Th1 cells correlates with clinical manifestations of disease. The cytokine IL-16 is a CD4+ T cell-specific chemoattractant that is biased towards CD4+ Th1 cells. IL-16 precursor is constitutively expressed in lymphocytes and during CD4+ T cell activation; active caspase-3 cleaves and releases C-terminal bioactive IL-16. Previously, we used an animal model of MS to demonstrate an important role for IL-16 in regulation of autoimmune inflammation and subsequent axonal damage. This role of IL-16 in MS is largely unexplored. Here we examine the regulation of IL-16 in relation to CD4+ Th1 infiltration and inflammation-related changes of axonal cytoskeleton in MS lesions. METHODS: We measured relative levels of IL-16, active caspase-3, T-bet, Stat-1 (Tyr (701)), and phosphorylated NF(M+H), in brain and spinal cord lesions from MS autopsies, using western blot analysis. We examined samples from 39 MS cases, which included acute, subacute and chronic lesions, as well as adjacent, normal-appearing white and grey matter. All samples were taken from patients with relapsing remitting clinical disease. We employed two-color immunostaining and confocal microscopy to identify phenotypes of IL-16-containing cells in frozen tissue sections from MS lesions. RESULTS: We found markedly increased levels of pro- and secreted IL-16 (80 kD and 22 kD, respectively) in MS lesions compared to controls. Levels of IL-16 peaked in acute, diminished in subacute, and were elevated again in chronic active lesions. Compared to lesions, lower but still appreciable IL-6 levels were measured in normal-appearing white matter adjacent to active lesions. Levels of IL-16 corresponded to increases in active-caspase-3, T-bet and phosphorylated Stat-1. In MS lesions, we readily observed IL-16 immunoreactivity confined to infiltrating CD3+, T-bet+ and active caspase-3+ mononuclear cells. CONCLUSION: We present evidence suggesting that IL-16 production occurs in MS lesions. We show correlations between increased levels of secreted IL-16, CD4+ Th1 cell inflammation, and phosphorylation of axonal cytoskeleton in MS lesions. Overall, the data suggest a possible role for IL-16 in regulation of inflammation and of subsequent changes in the axonal cytoskeleton in MS

Pre-encounter observations of 951 Gaspra

Photometry and colorimetry of 951 Gaspra were obtained on nine nights during the 1990 opposition. A composite lightcurve constructed using data from eight of those nights yielded a synodic rotational period of 7.04346 +/- 0.00006 hours, a mean absolute V magnitude of 11.8026 +/- 0.0025, and a slope parameter of 0.285 +/- 0.005. The apparent discrepancy can be easily resolved by realizing that their determination is based primarily on data obtained after opposition. Different phase functions pre- and post-opposition are a natural consequence of a changing aspect during an opposition. If the sub-Earth latitude on Gaspra is at a less equatorial aspect after opposition than it was before opposition, then we would expect to see a shallower phase function (corresponding to a larger numerical value of the slope parameter). Adding weight to this hypothesis is the last observation of the opposition, made in May after Gaspra had passed post opposition quadrature, which is displaced toward brighter absolute magnitudes relative to the rest of our data, indicating an even more poleward sub-Earth latitude than earlier in the opposition. Because the orbits of Earth and Gaspra are nearly coplanar, a substantial change in sub-Earth latitude during the opposition would not have been possible unless the obliquity of the asteroid's rotational axis is not small

X-ray pelvimetry in clinical obstetrics.

Journal ArticleX-ray pelvimetry has been used in obstetrics for over 80 years, but its clinical usefulness remains uncertain. Review of 101 consecutive x-ray pelvimetries obtained by Brown's modification of the Colcher-Sussman technique demonstrated the anteroposterior measurements to be of no value in predicting the eventual method of delivery. However, a transverse of the inlet of less than 13.0 cm and a transverse of the midpelvis of less than 10.0 cm were each associated with an increased frequency of operative delivery. In 94 cases no new information was obtained by x-ray pelvimetry; in the other 7 patients the information obtained was equally accessible by either ultrasonography or abdominal scout film. The authors conclude that x-ray pelvimetry by the technique used in their institution has very limited usefulness in clinical obstetrics

Origins of the Lunar and Planetary Laboratory, University of Arizona

The roots of the Lunar and Planetary Laboratory (LPL) extend deep into the rich fabric of G. P. Kuiper's view of the Earth as a planet and planetary systems as expected companions to most stars, as well as the post-war emergent technology of infrared detectors suitable for astronomy. These concepts and events began with Kuiper's theoretical work at Yerkes Observatory on the origin of the Solar System, his discovery of two planetary satellites and observational work with his near-infrared spectrometer on the then-new McDonald 82-inch telescope in the mid- to late-1940s. A grant for the production of a photographic atlas of the Moon in the mid-1950s enabled him to assemble the best existing images of the Moon and acquire new photographs. This brought E. A. Whitaker and D. W. G. Arthur to Yerkes. Others who joined in the lunar work were geologist Carl S. Huzzen and grad student E. P. Moore, as well as undergrad summer students A. B. Binder and D. P. Cruikshank (both in 1958). The Atlas was published in 1959, and work began on an orthographic lunar atlas. Kuiper's view of planetary science as an interdisciplinary enterprise encompassing astronomy, geology, and atmospheric physics inspired his vision of a research institution and an academic curriculum tuned to the combination of all the scientific disciplines embraced in a comprehensive study of the planets. Arrangements were made with the University of Arizona (UA) to establish LPL in affiliation with the widely recognized Inst. of Atmospheric Physics. Kuiper moved to the UA in late 1960, taking the lunar experts, graduate student T. C. Owen (planetary atmospheres), and associate B. M. Middlehurst along. G. van Biesbroeck also joined the migration to Tucson; Binder and Cruikshank followed along as new grad students. Astronomy grad student W. K. Hartmann came into the academic program at UA and the research group at LPL in 1961. Senior faculty affiliating with LPL in the earliest years were T. Gehrels, A. B. Meinel, H. L. Johnson, and F. J. Low, each with their own grad students and associates. Work began on IR spectroscopy and a rectified lunar atlas. Kuiper and Johnson started the search for future observatory sites in N. America and Hawaii

Role of IL-16 in CD4(+) T cell-mediated regulation of relapsing multiple sclerosis

In an important article published in Nature Medicine, Liu and colleagues described a novel CD4+ FoxA1+ regulatory T (Treg) cell population as distinct regulators of relapsing-remitting multiple sclerosis (RRMS) and experimental autoimmune encephalomyelitis (EAE). CD4+ FoxA1+ Treg cells appear as key regulators of responsiveness to therapy with interferon beta (IFN-β) in RRMS patients. Data indicate that CD4+ FoxA1+ FOXP3− Treg cells develop within the central nervous system (CNS), and a potential of cerebellar granule neurons (CGN) in generation of CD4+ FoxA1+ PD-L1hiFOXP3− Treg cells from encephalitogenic CD4+ T cells. A CD4 co-receptor specific ligand, IL-16, governs trafficking and biological properties of CD4+ T cells irrespective of their activation state. Functions of IL-16, relevant to Treg cells, include expansion of CD4+CD25+ T cells in long-term cultures with IL-2, de novo induction of FOXP-3 and migration of FOXP-3+ T cells. IL-16 is highly conserved across species including human and mouse. CGN and neurons in hippocampus contain neuronal-IL-16 (NIL-16), splice variant of immune IL-16, and express CD4 molecule. In a CD4-dependent manner, IL-16 supports cultured CGN survival. Concomitant studies of RRMS lesions and corresponding MOG35–55-induced relapsing EAE in (B6 × SJL)F1 (H-2b/s) mice discovered similar roles of IL-16 in regulation of relapsing disease. In RRMS and EAE relapse, peak levels of IL-16 and active caspase-3 correlated with CD4+ T cell infiltration and levels of T-bet, Stat-1(Tyr701), and phosphorylated neurofilaments of axonal cytoskeleton [NF (M + H) P], suggesting a role of locally produced IL-16 in regulation of CD4+ Th1 inflammation and axonal damage, respectively. IL-16 was abundantly present in CD4+ T cells, followed by CD20+ B, CD8+ T, CD83+ dendritic cells, and Mac-1+ microglia. Apart from lesions, bioactive IL-16 was located in normal-appearing white matter (NAWM) and normal-appearing grey matter (NAGM) in RRMS brain and spinal cord. A cytokine IL-16 emerges as an important regulator of relapsing MS and EAE. Better understanding of immune cell-neuron interactions mediated by IL-16 will foster development of more specific CD4+ T cell subset-targeted therapies to prevent or ameliorate progression of neuroinflammation and axonal and neuronal damage. Translational studies necessitate corresponding EAE models

The Spectrum of Pluto, 0.40 - 0.93 μ\mum I. Secular and longitudinal distribution of ices and complex organics

Context. During the last 30 years the surface of Pluto has been characterized, and its variability has been monitored, through continuous near-infrared spectroscopic observations. But in the visible range only few data are available. Aims. The aim of this work is to define the Pluto's relative reflectance in the visible range to characterize the different components of its surface, and to provide ground based observations in support of the New Horizons mission. Methods. We observed Pluto on six nights between May and July 2014, with the imager/spectrograph ACAM at the William Herschel Telescope (La Palma, Spain). The six spectra obtained cover a whole rotation of Pluto (Prot = 6.4 days). For all the spectra we computed the spectral slope and the depth of the absorption bands of methane ice between 0.62 and 0.90 $\mu$m. To search for shifts of the center of the methane bands, associated with dilution of CH4 in N2, we compared the bands with reflectances of pure methane ice. Results. All the new spectra show the methane ice absorption bands between 0.62 and 0.90 $\mu$m. The computation of the depth of the band at 0.62 $\mu$m in the new spectra of Pluto, and in the spectra of Makemake and Eris from the literature, allowed us to estimate the Lambert coefficient at this wavelength, at a temperature of 30 K and 40 K, never measured before. All the detected bands are blue shifted, with minimum shifts in correspondence with the regions where the abundance of methane is higher. This could be indicative of a dilution of CH4:N2 more saturated in CH4. The longitudinal and secular variations of the parameters measured in the spectra are in accordance with results previously reported in the literature and with the distribution of the dark and bright material that show the Pluto's albedo maps from New Horizons.Comment: This manuscript may change and improve during the reviewing process. The data reduction and calibration is reliable and has been checked independently using different reduction approaches. The data will be made publicily available when the paper is accepted. If you need them before, please, contact the autho

A Corticothalamic Switch: Controlling the Thalamus with Dynamic Synapses

SummaryCorticothalamic neurons provide massive input to the thalamus. This top-down projection may allow the cortex to regulate sensory processing by modulating the excitability of thalamic cells. Layer 6 corticothalamic neurons monosynaptically excite thalamocortical cells, but also indirectly inhibit them by driving inhibitory cells of the thalamic reticular nucleus. Whether corticothalamic activity generally suppresses or excites the thalamus remains unclear. Here we show that the corticothalamic influence is dynamic, with the excitatory-inhibitory balance shifting in an activity-dependent fashion. During low-frequency activity, corticothalamic effects are mainly suppressive, whereas higher-frequency activity (even a short bout of gamma frequency oscillations) converts the corticothalamic influence to enhancement. The mechanism of this switching depends on distinct forms of short-term synaptic plasticity across multiple corticothalamic circuit components. Our results reveal an activity-dependent mechanism by which corticothalamic neurons can bidirectionally switch the excitability and sensory throughput of the thalamus, possibly to meet changing behavioral demands

The Discovery of Cometary Activity in Near-Earth Asteroid (3552) Don Quixote

The near-Earth object (NEO) population, which mainly consists of fragments from collisions between asteroids in the main asteroid belt, is thought to include contributions from short-period comets as well. One of the most promising NEO candidates for a cometary origin is near-Earth asteroid (3552) Don Quixote, which has never been reported to show activity. Here we present the discovery of cometary activity in Don Quixote based on thermal-infrared observations made with the Spitzer Space Telescope in its 3.6 and 4.5 {\mu}m bands. Our observations clearly show the presence of a coma and a tail in the 4.5 {\mu}m but not in the 3.6 {\mu}m band, which is consistent with molecular band emission from CO2. Thermal modeling of the combined photometric data on Don Quixote reveals a diameter of 18.4 (-0.4/+0.3) km and an albedo of 0.03 (-0.01/+0.02), which confirms Don Quixote to be the third-largest known NEO. We derive an upper limit on the dust production rate of 1.9 kg s^-1 and derive a CO2 gas production rate of (1.1+-0.1)10^26 molecules s^-1. Spitzer IRS spectroscopic observations indicate the presence of fine-grained silicates, perhaps pyroxene rich, on the surface of Don Quixote. Our discovery suggests that CO2 can be present in near-Earth space over a long time. The presence of CO2 might also explain that Don Quixote's cometary nature remained hidden for nearly three decades.Comment: 40 pages, 8 figures, accepted by Ap