Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets

Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection

Gammaherpesvirus modulation of mouse adenovirus type 1 pathogenesis

AbstractImmune function is likely to be shaped by multiple infections over time. Infection with one pathogen can confer cross-protection against heterologous pathogens. We tested the hypothesis that latent murine gammaherpesvirus 68 (γHV68) infection modulates host inflammatory responses and susceptibility to mouse adenovirus type 1 (MAV-1). Mice were infected intranasally (i.n.) with γHV68. 21 days later, they were infected i.n. with MAV-1. We assessed cytokine and chemokine expression by quantitative reverse transcriptase real-time PCR, cellular inflammation by histology, and viral loads by quantitative real-time PCR. Previous γHV68 infection led to persistently upregulated IFN-γ in lungs and spleen and persistently upregulated CCL2 and CCL5 in the lungs. Previous γHV68 infection amplified MAV-1-induced CCL5 upregulation and cellular inflammation in the lungs. Previous γHV68 infection was associated with lower MAV-1 viral loads in the spleen but not the lung. There was no significant effect of previous γHV68 on IFN-γ expression or MAV-1 viral loads when the interval between infections was increased to 44 days. In summary, previous γHV68 infection modulated lung inflammatory responses and decreased susceptibility to a heterologous virus in an organ- and time-dependent manner

Gut Dysbiosis Promotes M2 Macrophage Polarization and Allergic Airway Inflammation via Fungi-Induced PGE2

SummaryAlthough imbalances in gut microbiota composition, or “dysbiosis,” are associated with many diseases, the effects of gut dysbiosis on host systemic physiology are less well characterized. We report that gut dysbiosis induced by antibiotic (Abx) treatment promotes allergic airway inflammation by shifting macrophage polarization in the lung toward the alternatively activated M2 phenotype. Adoptive transfer of alveolar macrophages derived from Abx-treated mice was sufficient to increase allergic airway inflammation. Abx treatment resulted in the overgrowth of a commensal fungal Candida species in the gut and increased plasma concentrations of prostaglandin E2 (PGE2), which induced M2 macrophage polarization in the lung. Suppression of PGE2 synthesis by the cyclooxygenase inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and decreased allergic airway inflammatory cell infiltration in Abx-treated mice. Thus, Abx treatment can cause overgrowth of particular fungal species in the gut and promote M2 macrophage activation at distant sites to influence systemic responses including allergic inflammation

The Size and Shape of Voids in Three-Dimensional Galaxy Surveys

The sizes and shapes of voids in a galaxy survey depend not only on the physics of structure formation, but also on the sampling density of the survey and on the algorithm used to define voids. Using an N-body simulation with a CDM power spectrum, we study the properties of voids in samples with different number densities of galaxies, both in redshift space and in real space. When voids are defined as regions totally empty of galaxies, their characteristic volume is strongly dependent on sampling density; when they are defined as regions whose density is 0.2 times the mean galaxy density, the dependence is less strong. We compare two void-finding algorithms, one in which voids are nonoverlapping spheres, and one, based on the algorithm of Aikio and Mahonen, which does not predefine the shape of a void. Regardless of the algorithm chosen, the characteristic void size is larger in redshift space than in real space, and is larger for low sampling densities than for high sampling densities. We define an elongation statistic Q which measures the tendency of voids to be stretched or squashed along the line of sight. Using this statistic, we find that at sufficiently high sampling densities (comparable to the number densities of galaxies brighter than L_*), large voids tend to be slightly elongated along the line of sight in redshift space.Comment: LaTex, 21 pages (including 7 figures), ApJ, submitte

Demand-Driven Scheduling of Movies in a Multiplex

This paper describes a model that generates weekly movie schedules in a multiplex movie theater. A movie schedule specifies within each day of the week, on which screen(s) different movies will be played, and at which time(s). The model consists of two parts: (i) conditional forecasts of the number of visitors per show for any possible starting time; and (ii) an optimization procedure that quickly finds an almost optimal schedule (which can be demonstrated to be close to the optimal schedule). To generate this schedule we formulate the so-called movie scheduling problem as a generalized set partitioning problem. The latter is solved with an algorithm based on column generation techniques. We have applied this combined demand forecasting /schedule optimization procedure to a multiplex in Amsterdam where we supported the scheduling of fourteen movie weeks. The proposed model not 2 only makes movie scheduling easier and less time consuming, but also generates schedules that would attract more visitors than the current ‘intuition-based’ schedules

Limited effects of Muc1 deficiency on mouse adenovirus type 1 respiratory infection

Muc1 (MUC1 in humans) is a membrane-tethered mucin that exerts anti-inflammatory effects in the lung during bacterial infection. Muc1 and other mucins are also likely to form a protective barrier in the lung. We used mouse adenovirus type 1 (MAV-1, also known as MAdV-1) to determine the role of Muc1 in the pathogenesis of an adenovirus in its natural host. Following intranasal inoculation of wild type mice, we detected increased TNF-α, a cytokine linked to Muc1 production, but no consistent changes in the production of lung Muc1, Muc5ac or overall lung mucus production. Viral loads were modestly higher in the lungs of Muc1−/− mice compared to Muc1+/+ mice at several early time points but decreased to similar levels by 14 days post infection in both groups. However, cellular inflammation and the expression of CXCL1, CCL5, and CCL2 did not significantly differ between Muc1−/− and Muc1+/+ mice. Our data therefore suggest that Muc1 may contribute to a physical barrier that protects against MAV-1 respiratory infection. However, our data do not reveal an anti-inflammatory effect of Muc1 that contributes to MAV-1 pathogenesis.

Vacuum Energy Cancellation in a Non-supersymmetric String

We present a nonsupersymmetric orbifold of type II string theory and show that it has vanishing cosmological constant at the one and two loop level. We argue heuristically that the cancellation persists at higher loops.Comment: 31 pages harvmac big, 6 figures. New version includes the 2-loop analysis of hep-th/9810129 and elimination of one of the two heuristic arguments for higher loop cancellatio

Dihydropyrimidine Accumulation Is Required for the Epithelial-Mesenchymal Transition

It is increasingly appreciated that oncogenic transformation alters cellular metabolism to facilitate cell proliferation, but less is known about the metabolic changes that promote cancer cell aggressiveness. Here, we analyzed metabolic gene expression in cancer cell lines and found that a set of high-grade carcinoma lines expressing mesenchymal markers share a unique 44 gene signature, designated the “mesenchymal metabolic signature” (MMS). A FACS-based shRNA screen identified several MMS genes as essential for the epithelial-mesenchymal transition (EMT), but not for cell proliferation. Dihydropyrimidine dehydrogenase (DPYD), a pyrimidine-degrading enzyme, was highly expressed upon EMT induction and was necessary for cells to acquire mesenchymal characteristics in vitro and for tumorigenic cells to extravasate into the mouse lung. This role of DPYD was mediated through its catalytic activity and enzymatic products, the dihydropyrimidines. Thus, we identify metabolic processes essential for the EMT, a program associated with the acquisition of metastatic and aggressive cancer cell traits.United States. National Institutes of Health (RO1 CA103866)United States. National Institutes of Health (AI047389)United States. National Institutes of Health (K99 CA168940)American Cancer Society (PF-12-099-01-TGB)American Cancer Society (PF-13-356-01-TBE)United States. Department of Defense (BC123066)United States. National Institutes of Health (CA112967)United States. National Institutes of Health (ES015339

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected