Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs.

Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures

A T8.5 Brown Dwarf Member of the Xi Ursae Majoris System

The Wide-field Infrared Survey Explorer has revealed a T8.5 brown dwarf (WISE J111838.70+312537.9) that exhibits common proper motion with a solar-neighborhood (8 pc) quadruple star system - Xi Ursae Majoris. The angular separation is 8.5 arc-min, and the projected physical separation is about 4000 AU. The sub-solar metallicity and low chromospheric activity of Xi UMa A argue that the system has an age of at least 2 Gyr. The infrared luminosity and color of the brown dwarf suggests the mass of this companion ranges between 14 and 38 Jupiter masses for system ages of 2 and 8 Gyr respectively.Comment: AJ in press, 12 pages LaTeX with 6 figures. More astrometric data and a laser guide star adaptive optics image adde

Ultrafast coherent manipulation of trions in site-controlled nanowire quantum dots

Physical implementations of large-scale quantum processors based on solid-state platforms benefit from realizations of quantum bits positioned in regular arrays. Self-assembled quantum dots are well established as promising candidates for quantum optics and quantum information processing, but they are randomly positioned. Site-controlled quantum dots, on the other hand, are grown in pre-defined locations but have not yet been sufficiently developed to be used as a platform for quantum information processing. In this paper, we demonstrate all-optical ultrafast complete coherent control of a qubit formed by the single-spin/trion states of a charged site-controlled nanowire quantum dot. Our results show that site-controlled quantum dots in nanowires are promising hosts of charged-exciton qubits and that these qubits can be cleanly manipulated in the same fashion as has been demonstrated in randomly positioned quantum dot samples. Our findings suggest that many of the related excitonic qubit experiments that have been performed over the past 15 years may work well in the more scalable, site-controlled systems, making them very promising for the realization of quantum hardware

Hodgkin's lymphoma presenting with markedly elevated IgE: a case report

<p>Abstract</p> <p>Background</p> <p>Markedly elevated IgE as a manifestation of a lymphoproliferative disorder has been only rarely reported.</p> <p>Case Presentation</p> <p>We present the case of a 22 year old female referred to the adult Allergy & Clinical Immunology clinic for an extremely elevated IgE level, eventually diagnosed with Hodgkin's lymphoma. She had no history of atopy, recurrent infections, eczema or periodontal disease; stool was negative for ova & parasites. Chest X-ray revealed large bilateral anterior mediastinal masses that demonstrated prominent uptake on gallium scan. Mediastinal lymph node biopsy was consistent with Hodgkin's lymphoma, nodular sclerosing subtype, grade I/II.</p> <p>Conclusion</p> <p>Although uncommon, markedly elevated IgE may be a manifestation of a malignant process, most notably both Hodgkin's and Non-Hodgkin's lymphomas. This diagnosis should be considered in evaluating an otherwise unexplained elevation of IgE.</p

Association of SNPs in EGR3 and ARC with schizophrenia supports a biological pathway for schizophrenia risk

We have previously hypothesized a biological pathway of activity-dependent synaptic plasticity proteins that addresses the dual genetic and environmental contributions to schizophrenia. Accordingly, variations in the immediate early gene EGR3, and its target ARC, should influence schizophrenia susceptibility. We used a pooled Next-Generation Sequencing approach to identify variants across these genes in U.S. populations of European (EU) and African (AA) descent. Three EGR3 and one ARC SNP were selected and genotyped for validation, and three SNPs were tested for association in a replication cohort. In the EU group of 386 schizophrenia cases and 150 controls EGR3 SNP rs1877670 and ARC SNP rs35900184 showed significant associations (p = 0.0078 and p = 0.0275, respectively). In the AA group of 185 cases and 50 controls, only the ARC SNP revealed significant association (p = 0.0448). The ARC SNP did not show association in the Han Chinese (CH) population. However, combining the EU, AA, and CH groups revealed a highly significant association of ARC SNP rs35900184 (p = 2.353 x 10(-7); OR [95% CI] = 1.54 [1.310-1.820]). These findings support previously reported associations between EGR3 and schizophrenia. Moreover, this is the first report associating an ARC SNP with schizophrenia and supports recent large-scale GWAS findings implicating the ARC complex in schizophrenia risk. These results support the need for further investigation of the proposed pathway of environmentally responsive, synaptic plasticity-related, schizophrenia genes

Excitation Mechanisms for HCN (1-0) and HCO+ (1-0) in Galaxies from the Great Observatories All-sky LIRG Survey

We present new Institut de Radioastronomie Millimétrique (IRAM) 30 m spectroscopic observations of the ~88 GHz band, including emission from the CCH (N = 1 → 0) multiplet, HCN (J = 1 → 0), HCO^+ (J = 1 → 0), and HNC(J = 1 → 0), for a sample of 58 local luminous and ultraluminous infrared galaxies from the Great Observatories All-sky LIRG Survey (GOALS). By combining our new IRAM data with literature data and Spitzer/IRS spectroscopy, we study the correspondence between these putative tracers of dense gas and the relative contribution of active galactic nuclei (AGNs) and star formation to the mid-infrared luminosity of each system. We find the HCN (1–0) emission to be enhanced in AGN-dominated systems (〈L'_(HCN(1-0))/L'_(HCN(1-0)^+(1-0)〉 =1.84), compared to composite and starburst-dominated systems 〈L'_(HCN(1-0))/L'_(HCN(1-0)^+(1-0)〉 = 1.14, and 0.88, respectively). However, some composite and starburst systems have 〈L'_(HCN(1-0))/L'_(HCN(1-0)^+(1-0)〉 ratios comparable to those of AGNs, indicating that enhanced HCN emission is not uniquely associated with energetically dominant AGNs. After removing AGN-dominated systems from the sample, we find a linear relationship (within the uncertainties) between log10 〈L'_(HCN(1-0))/L'_(HCN(1-0)^+(1-0)〉 and log10(L_(IR)), consistent with most previous findings. L'_(HCN(1-0))/L_(IR), typically interpreted as the dense-gas depletion time, appears to have no systematic trend with LIR for our sample of luminous and ultraluminous infrared galaxies, and has significant scatter. The galaxy-integrated L'_(HCN(1-0)) and L'_(HCN^+(1-0)) emission do not appear to have a simple interpretation in terms of the AGN dominance or the star formation rate, and are likely determined by multiple processes, including density and radiative effects

In vivo and in vitro studies of Th17 response to specific immunotherapy in house dust mite-induced allergic rhinitis patients

10.1371/journal.pone.0091950PLoS ONE93-POLN

What have transgenic and knockout animals taught us about respiratory disease?

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease