Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3) by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer\u27s disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson\u27s disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain

Diesel Exhaust Activates & Primes Microglia: Air Pollution, Neuroinflammation, & Regulation of Dopaminergic Neurotoxicity

BACKGROUND: Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood. OBJECTIVES: Here, we sought to address the brain-region-specific effects of diesel exhaust (DE) and key cellular mechanisms underlying DE-induced microglia activation, neuroinflammation, and dopaminergic (DA) neurotoxicity. METHODS: Rats were exposed to DE (2.0, 0.5, and 0 mg/m3) by inhalation over 4 weeks or as a single intratracheal administration of DE particles (DEP; 20 mg/kg). Primary neuron-glia cultures and the HAPI (highly aggressively proliferating immortalized) microglial cell line were used to explore cellular mechanisms. RESULTS: Rats exposed to DE by inhalation demonstrated elevated levels of whole-brain IL-6 (interleukin-6) protein, nitrated proteins, and IBA-1 (ionized calcium-binding adaptor molecule 1) protein (microglial marker), indicating generalized neuroinflammation. Analysis by brain region revealed that DE increased TNFα (tumor necrosis factor-α), IL-1β, IL-6, MIP-1α (macrophage inflammatory protein-1α) RAGE (receptor for advanced glycation end products), fractalkine, and the IBA-1 microglial marker in most regions tested, with the midbrain showing the greatest DE response. Intratracheal administration of DEP increased microglial IBA-1 staining in the substantia nigra and elevated both serum and whole-brain TNFα at 6 hr posttreatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 μg/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNFα release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 μg/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity. CONCLUSIONS: Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity

Long-term Periodicities of Cataclysmic Variables with Synoptic Surveys

A systematic study on the long-term periodicities of known Galactic cataclysmic variables (CVs) was conducted. Among 1580 known CVs, 344 sources were matched and extracted from the Palomar Transient Factory (PTF) data repository. The PTF light curves were combined with the Catalina Real-Time Transient Survey (CRTS) light curves and analyzed. Ten targets were found to exhibit long-term periodic variability, which is not frequently observed in the CV systems. These long-term variations are possibly caused by various mechanisms, such as the precession of the accretion disk, hierarchical triple star system, magnetic field change of the companion star, and other possible mechanisms. We discuss the possible mechanisms in this study. If the long-term period is less than several tens of days, the disk precession period scenario is favored. However, the hierarchical triple star system or the variations in magnetic field strengths are most likely the predominant mechanisms for longer periods.Comment: 33 pages, 9 figures (manuscript form), Accepted for publication in PAS

Diesel Exhaust Activates and Primes Microglia: Air Pollution, Neuroinflammation, and Regulation of Dopaminergic Neurotoxicity

Background: Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood

Photometric redshifts in the SWIRE Survey

We present the SWIRE Photometric Redshift Catalogue, 1025119 redshifts of unprecedented reliability and accuracy. Our method is based on fixed galaxy and QSO templates applied to data at 0.36-4.5 mu, and on a set of 4 infrared emission templates fitted to infrared excess data at 3.6-170 mu. The code involves two passes through the data, to try to optimize recognition of AGN dust tori. A few carefully justified priors are used and are the key to supression of outliers. Extinction, A_V, is allowed as a free parameter. We use a set of 5982 spectroscopic redshifts, taken from the literature and from our own spectroscopic surveys, to analyze the performance of our method as a function of the number of photometric bands used in the solution and the reduced chi^2. For 7 photometric bands the rms value of (z_{phot}-z_{spec})/(1+z_{spec}) is 3.5%, and the percentage of catastrophic outliers is ~1%. We discuss the redshift distributions at 3.6 and 24 mu. In individual fields, structure in the redshift distribution corresponds to clusters which can be seen in the spectroscopic redshift distribution. 10% of sources in the SWIRE photometric redshift catalogue have z >2, and 4% have z>3, so this catalogue is a huge resource for high redshift galaxies. A key parameter for understanding the evolutionary status of infrared galaxies is L_{ir}/L_{opt}, which can be interpreted as the specific star-formation rate for starbursts. For dust tori around Type 1 AGN, L_{tor}/L_{opt} is a measure of the torus covering factor and we deduce a mean covering factor of 40%.Comment: 22 pages, 23 figures. Accepted for publication in MNRAS. Revised 28/2/08. Version with figures at full resolution at http://astro.ic.ac.uk/~mrr/swirephotzcat/swirephotz5.pdf.g

The Spitzer Survey of Stellar Structure in Galaxies (S^4G)

The Spitzer Survey of Stellar Structure in Galaxies S^4G is an Exploration Science Legacy Program approved for the Spitzer post-cryogenic mission. It is a volume-, magnitude-, and size-limited (d < 40 Mpc, |b| > 30 degrees, m_(Bcorr) < 15.5, D25>1') survey of 2,331 galaxies using IRAC at 3.6 and 4.5 microns. Each galaxy is observed for 240 s and mapped to > 1.5 x D25. The final mosaicked images have a typical 1 sigma rms noise level of 0.0072 and 0.0093 MJy / sr at 3.6 and 4.5 microns, respectively. Our azimuthally-averaged surface brightness profile typically traces isophotes at mu_3.6 (AB) (1 sigma) ~ 27 mag arcsec^-2, equivalent to a stellar mass surface density of ~ 1 Msun pc^-2. S^4G thus provides an unprecedented data set for the study of the distribution of mass and stellar structures in the local Universe. This paper introduces the survey, the data analysis pipeline and measurements for a first set of galaxies, observed in both the cryogenic and warm mission phase of Spitzer. For every galaxy we tabulate the galaxy diameter, position angle, axial ratio, inclination at mu_3.6 (AB) = 25.5 and 26.5 mag arcsec^-2 (equivalent to ~ mu_B (AB) =27.2 and 28.2 mag arcsec^-2, respectively). These measurements will form the initial S^4G catalog of galaxy properties. We also measure the total magnitude and the azimuthally-averaged radial profiles of ellipticity, position angle, surface brightness and color. Finally, we deconstruct each galaxy using GALFIT into its main constituent stellar components: the bulge/spheroid, disk, bar, and nuclear point source, where necessary. Together these data products will provide a comprehensive and definitive catalog of stellar structures, mass and properties of galaxies in the nearby Universe.Comment: Accepted for Publication in PASP, 14 pages, 13 figure

ChAInGeS: The Chandra Arp Interacting Galaxies Survey

We have conducted a statistical analysis of the ultra-luminous X-ray point sources (ULXs; L(X) >= 10^39 erg/s) in a sample of galaxies selected from the Arp Atlas of Peculiar Galaxies. We find a possible enhancement of a factor of ~2-4 in the number of ULXs per blue luminosity for the strongly interacting subset. Such an enhancement would be expected if ULX production is related to star formation, as interacting galaxies tend to have enhanced star formation rates on average. For most of the Arp galaxies in our sample, the total number of ULXs compared to the far-infrared luminosity is consistent with values found earlier for spiral galaxies. This suggests that for these galaxies, ULXs trace recent star formation. However, for the most infrared-luminous galaxies, we find a deficiency of ULXs compared to the infrared luminosity. For these very infrared-luminous galaxies, AGNs may contribute to powering the far-infrared; alternatively, ULXs may be highly obscured in the X-ray in these galaxies and therefore not detected by these Chandra observations. We determined local UV/optical colors within the galaxies in the vicinity of the candidate ULXs using GALEX UV and SDSS optical images. In most cases, the distributions of colors are similar to the global colors of interacting galaxies. However, the u - g and r - i colors at the ULX locations tend to be bluer on average than these global colors, suggesting that ULXs are preferentially found in regions with young stellar populations. In the Arp sample there is a possible enhancement of a factor of ~2 - 5 in the fraction of galactic nuclei that are X-ray bright compared to more normal spirals.Comment: 28 pages, 7 figures, Astronomical Journal, in pres

High-Redshift QSOs in the SWIRE Survey and the z~3 QSO Luminosity Function

We use a simple optical/infrared (IR) photometric selection of high-redshift QSOs that identifies a Lyman Break in the optical photometry and requires a red IR color to distinguish QSOs from common interlopers. The search yields 100 z~3 (U-dropout) QSO candidates with 19<r'<22 over 11.7 deg^2 in the ELAIS-N1 (EN1) and ELAIS-N2 (EN2) fields of the Spitzer Wide-area Infrared Extragalactic (SWIRE) Legacy Survey. The z~3 selection is reliable, with spectroscopic follow-up of 10 candidates confirming they are all QSOs at 2.83<z<3.44. We find that our z~4$ (g'-dropout) sample suffers from both unreliability and incompleteness but present 7 previously unidentified QSOs at 3.50<z<3.89. Detailed simulations show our z~3 completeness to be ~80-90% from 3.0<z<3.5, significantly better than the ~30-80% completeness of the SDSS at these redshifts. The resulting luminosity function extends two magnitudes fainter than SDSS and has a faint end slope of beta=-1.42 +- 0.15, consistent with values measured at lower redshift. Therefore, we see no evidence for evolution of the faint end slope of the QSO luminosity function. Including the SDSS QSO sample, we have now directly measured the space density of QSOs responsible for ~70% of the QSO UV luminosity density at z~3. We derive a maximum rate of HI photoionization from QSOs at z~3.2, Gamma = 4.8x10^-13 s^-1, about half of the total rate inferred through studies of the Ly-alpha forest. Therefore, star-forming galaxies and QSOs must contribute comparably to the photoionization of HI in the intergalactic medium at z~3.Comment: Accepted for publication in ApJ. emulateapj format. 23 pages, 17 figure

Hα star formation main sequence in cluster and field galaxies at z ∼ 1.6

We calculate Hα-based star formation rates and determine the star formation rate–stellar mass relation for members of three Spitzer Adaptation of the Red-Sequence Cluster Survey (SpARCS) clusters at z ∼ 1.6 and serendipitously identified field galaxies at similar redshifts to the clusters. We find similar star formation rates in cluster and field galaxies throughout our range of stellar masses. The results are comparable to those seen in other clusters at similar redshifts, and consistent with our previous photometric evidence for little quenching activity in clusters. One possible explanation for our results is that galaxies in our z ∼ 1.6 clusters have been accreted too recently to show signs of environmental quenching. It is also possible that the clusters are not yet dynamically mature enough to produce important environmental quenching effects shown to be important at low redshift, such as ram-pressure stripping or harassment

The Society for Immunotherapy of Cancer statement on best practices for multiplex immunohistochemistry (IHC) and immunofluorescence (IF) staining and validation.

OBJECTIVES: The interaction between the immune system and tumor cells is an important feature for the prognosis and treatment of cancer. Multiplex immunohistochemistry (mIHC) and multiplex immunofluorescence (mIF) analyses are emerging technologies that can be used to help quantify immune cell subsets, their functional state, and their spatial arrangement within the tumor microenvironment. METHODS: The Society for Immunotherapy of Cancer (SITC) convened a task force of pathologists and laboratory leaders from academic centers as well as experts from pharmaceutical and diagnostic companies to develop best practice guidelines for the optimization and validation of mIHC/mIF assays across platforms. RESULTS: Representative outputs and the advantages and disadvantages of mIHC/mIF approaches, such as multiplexed chromogenic IHC, multiplexed immunohistochemical consecutive staining on single slide, mIF (including multispectral approaches), tissue-based mass spectrometry, and digital spatial profiling are discussed. CONCLUSIONS: mIHC/mIF technologies are becoming standard tools for biomarker studies and are likely to enter routine clinical practice in the near future. Careful assay optimization and validation will help ensure outputs are robust and comparable across laboratories as well as potentially across mIHC/mIF platforms. Quantitative image analysis of mIHC/mIF output and data management considerations will be addressed in a complementary manuscript from this task force