SJL Mice Infected with Acanthamoeba castellanii Develop Central Nervous System Autoimmunity through the Generation of Cross-Reactive T Cells for Myelin Antigens

We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139–151 and myelin basic protein 89–101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139–151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139–151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, and they can transfer disease to naïve animals. Likewise, the animals first primed with suboptimal dose of PLP 139–151 and later infected with ACA, developed EAE, suggesting that ACA infection can trigger CNS autoimmunity in the presence of preexisting repertoire of autoreactive T cells. Taken together, the data provide novel insights into the pathogenesis of Acanthamoeba infections, and the potential role of infectious agents with mimicry epitopes to self-antigens in the pathogenesis of CNS diseases such as multiple sclerosis

ESO Imaging Survey. The Stellar Catalogue in the Chandra Deep Field South

(abridged) Stellar catalogues in five passbands (UBVRI) over an area of approximately 0.3 deg^2, comprising about 1200 objects, and in seven passbands (UBVRIJK) over approximately 0.1 deg^2, comprising about 400 objects, in the direction of the Chandra Deep Field South are presented. The 90% completeness level of the number counts is reached at approximately U = 23.8, B = 24.0, V = 23.5, R = 23.0, I = 21.0, J = 20.5, K = 19.0. A scheme is presented to select point sources from these catalogues, by combining the SExtractor parameter CLASS_STAR from all available passbands. Probable QSOs and unresolved galaxies are identified by using the previously developed \chi^2-technique (Hatziminaoglou et al 2002), that fits the overall spectral energy distributions to template spectra and determines the best fitting template. The observed number counts, colour-magnitude diagrams, colour-colour diagrams and colour distributions are presented and, to judge the quality of the data, compared to simulations based on the predictions of a Galactic Model convolved with the estimated completeness functions and the error model used to describe the photometric errors of the data. The resulting stellar catalogues and the objects identified as likely QSOs and unresolved galaxies with coordinates, observed magnitudes with errors and assigned spectral types by the $\chi^2$-technique are presented and are publicly available.Comment: Paper as it will appear in print. Complete figures and tables can be obtained from: http://www.eso.org/science/eis/eis_pub/eis_pub.html. Astronomy & Astrophysics, accepted for publicatio

Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension

Aims Growing evidence suggests that arginase misregulation plays a key role in the pathophysiology of essential hypertension. In the present study, we investigated the potential cardiovascular therapeutic effects of a long-term treatment with an arginase inhibitor in adult spontaneously hypertensive rats (SHR) with fully developed hypertension. Methods and results Treatment of 25-week-old SHR with the arginase inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA, 40 mg/day for 10 weeks) sustainably reduced systolic blood pressure (−30 mmHg, P < 0.05). The antihypertensive effect of nor-NOHA was associated with changes on mesenteric artery reactivity including the restoration of angiotensin-II-induced contraction and acetylcholine-induced vasodilation to the values of normotensive Wistar Kyoto rats. Both nitric oxide synthase and cyclooxygenase-dependent mechanisms account for the improvement of endothelial function afforded by the arginase inhibitor, which in addition blunted hypertension-induced endothelial arginase I overexpression in mesenteric arteries. Nor-NOHA also prevented the remodelling of aorta as measured by collagen content and media/lumen ratio, and improved the compliance of carotid artery in SHR. Cardiac fibrosis assessed by collagen content of left heart ventricle was reduced by nor-NOHA, with no significant effect on cardiac hypertrophy. Conclusion Our results report that a long-term treatment with an arginase inhibitor reduced blood pressure, improved vascular function, and reduced cardiac fibrosis in SHR with fully developed hypertension. These data suggest that arginase represents a promising novel target for pharmacological intervention in essential hypertensio

Secular evolution versus hierarchical merging: galaxy evolution along the Hubble sequence, in the field and rich environments

In the current galaxy formation scenarios, two physical phenomena are invoked to build disk galaxies: hierarchical mergers and more quiescent external gas accretion, coming from intergalactic filaments. Although both are thought to play a role, their relative importance is not known precisely. Here we consider the constraints on these scenarios brought by the observation-deduced star formation history on the one hand, and observed dynamics of galaxies on the other hand: the high frequency of bars and spirals, the high frequency of perturbations such as lopsidedness, warps, or polar rings. All these observations are not easily reproduced in simulations without important gas accretion. N-body simulations taking into account the mass exchange between stars and gas through star formation and feedback, can reproduce the data, only if galaxies double their mass in about 10 Gyr through gas accretion. Warped and polar ring systems are good tracers of this accretion, which occurs from cold gas which has not been virialised in the system's potential. The relative importance of these phenomena are compared between the field and rich clusters. The respective role of mergers and gas accretion vary considerably with environment.Comment: 18 pages, 8 figures, review paper to "Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuning Fork Strikes a New Note", Pilanesberg, ed. D. Block et al., Kluwe

IPTF Search for An Optical Counterpart to Gravitational-Wave TransientT GW150914

The American Astronomical Society. All rights reserved..The intermediate Palomar Transient Factory (iPTF) autonomously responded to and promptly tiled the error region of the first gravitational-wave event GW150914 to search for an optical counterpart. Only a small fraction of the total localized region was immediately visible in the northern night sky, due both to Sun-angle and elevation constraints. Here, we report on the transient candidates identified and rapid follow-up undertaken to determine the nature of each candidate. Even in the small area imaged of 126 deg2, after extensive filtering, eight candidates were deemed worthy of additional follow-up. Within two hours, all eight were spectroscopically classified by the Keck II telescope. Curiously, even though such events are rare, one of our candidates was a superluminous supernova. We obtained radio data with the Jansky Very Large Array and X-ray follow-up with the Swift satellite for this transient. None of our candidates appear to be associated with the gravitational-wave trigger, which is unsurprising given that GW150914 came from the merger of two stellar-mass black holes. This end-to-end discovery and follow-up campaign bodes well for future searches in this post-detection era of gravitational waves

Quantum Correlations in NMR systems

In conventional NMR experiments, the Zeeman energy gaps of the nuclear spin ensembles are much lower than their thermal energies, and accordingly exhibit tiny polarizations. Generally such low-purity quantum states are devoid of quantum entanglement. However, there exist certain nonclassical correlations which can be observed even in such systems. In this chapter, we discuss three such quantum correlations, namely, quantum contextuality, Leggett-Garg temporal correlations, and quantum discord. In each case, we provide a brief theoretical background and then describe some results from NMR experiments.Comment: 21 pages, 7 figure

Evolution of interstellar dust and stardust in the solar neighbourhood

The abundance evolution of interstellar dust species originating from stellar sources and from condensation in molecular clouds in the local interstellar medium of the Milky Way is studied and the input of dust material to the Solar System is determined. A one-zone chemical evolution model of the Milky Way for the elemental composition of the disk combined with an evolution model for its interstellar dust component similar to that of Dwek (1998) is developed. The dust model considers dust-mass return from AGB stars as calculated from synthetic AGB models combined with models for dust condensation in stellar outflows. Supernova dust formation is included in a simple parameterized form which is gauged by observed abundances of presolar dust grains with supernova origin. For dust growth in the ISM a simple method is developed for coupling this with disk and dust evolution models. The time evolution of the abundance of the following dust species is followed in the model: silicate, carbon, silicon carbide, and iron dust from AGB stars and from SNe as well as silicate, carbon, and iron dust grown in molecular clouds. It is shown that the interstellar dust population is dominated by dust accreted in molecular clouds; most of the dust material entering the Solar System at its formation does not show isotopic abundance anomalies of the refractory elements, i.e., inconspicuous isotopic abundances do not point to a Solar System origin of dust grains. The observed abundance ratios of presolar dust grains formed in SN ejecta and in AGB star outflows requires that for the ejecta from SNe the fraction of refractory elements condensed into dust is 0.15 for carbon dust and is quite small ($\sim10^{-4}$) for other dust species.Comment: 29 pages, 19 figure

Re-examining the Unified Theory of Acceptance and Use of Technology (UTAUT): Towards a Revised Theoretical Model

YesBased on a critical review of the Unified Theory of Acceptance and Use of Technology (UTAUT), this study first formalized an alternative theoretical model for explaining the acceptance and use of information system (IS) and information technology (IT) innovations. The revised theoretical model was then empirically examined using a combination of meta-analysis and structural equation modelling (MASEM) techniques. The meta-analysis was based on 1600 observations on 21 relationships coded from 162 prior studies on IS/IT acceptance and use. The SEM analysis showed that attitude: was central to behavioural intentions and usage behaviours, partially mediated the effects of exogenous constructs on behavioural intentions, and had a direct influence on usage behaviours. A number of implications for theory and practice are derived based on the findings

Distinct Regions of the Large Extracellular Domain of Tetraspanin CD9 Are Involved in the Control of Human Multinucleated Giant Cell Formation

Multinucleated giant cells, formed by the fusion of monocytes/macrophages, are features of chronic granulomatous inflammation associated with infections or the persistent presence of foreign material. The tetraspanins CD9 and CD81 regulate multinucleated giant cell formation: soluble recombinant proteins corresponding to the large extracellular domain (EC2) of human but not mouse CD9 can inhibit multinucleated giant cell formation, whereas human CD81 EC2 can antagonise this effect. Tetraspanin EC2 are all likely to have a conserved three helix sub-domain and a much less well-conserved or hypervariable sub-domain formed by short helices and interconnecting loops stabilised by two or more disulfide bridges. Using CD9/CD81 EC2 chimeras and point mutants we have mapped the specific regions of the CD9 EC2 involved in multinucleated giant cell formation. These were primarily located in two helices, one in each sub-domain. The cysteine residues involved in the formation of the disulfide bridges in CD9 EC2 were all essential for inhibitory activity but a conserved glycine residue in the tetraspanin-defining ‘CCG’ motif was not. A tyrosine residue in one of the active regions that is not conserved between human and mouse CD9 EC2, predicted to be solvent-exposed, was found to be only peripherally involved in this activity. We have defined two spatially-distinct sites on the CD9 EC2 that are required for inhibitory activity. Agents that target these sites could have therapeutic applications in diseases in which multinucleated giant cells play a pathogenic role