The Role of Inflammatory Monocytes in Post-Influenza Methicillin-Resistant Staphylococcus aureus Pneumonia

Secondary bacterial infections following influenza can lead to poor clinical outcomes and mortality. It is widely accepted that susceptibility to secondary bacterial infections is attributable to a suppressed innate antibacterial immunity. In contrast, a dysregulated host inflammatory response may also contribute to disease severity. Inflammation induced by viral infection alone significantly affects lung pathology, potentially exacerbating the destruction of the respiratory tract. Interestingly, the role of inflammatory mediators such as inflammatory monocytes have been extensively studied during influenza infection alone; however, their role during secondary bacterial infection are still not fully established. The objective of this study was to analyze the contribution of inflammatory monocytes during secondary S. aureus infection and their effect on lung pathology. Based on the negative impact of inflammatory monocytes during influenza infection alone, and their little recruitment during S. aureus infection alone, we hypothesized that inflammatory monocytes contribute to increased mortality and lung pathology during secondary MRSA pneumonia. In order to study the possible effects of inflammatory monocytes, we developed post-influenza MRSA pneumonia murine models, with and without antibiotic treatment, using mice deficient in the chemokine receptor, C-C chemokine receptor type 2 (CCR2). Interestingly, we found that CCR2-deficient (CCR2-/-) mice, which are unable to sufficiently recruit inflammatory monocytes to the airways, survive significantly better compared to WT mice after post-influenza MRSA infection. Furthermore, we show, mechanistically, that inflammatory monocytes may impair the phagocytic bacterial killing function of alveolar macrophages, leading to decreased bacterial clearance and increased mortality. Future studies will evaluate the effect of inflammatory monocytes on lung damage during post-influenza MRSA pneumonia

HST Scattered Light Imaging and Modeling of the Edge-on Protoplanetary Disk ESO-Hα\alpha 569

We present new HST ACS observations and detailed models for a recently discovered edge-on protoplanetary disk around ESO H$\alpha$ 569 (a low-mass T Tauri star in the Cha I star forming region). Using radiative transfer models we probe the distribution of the grains and overall shape of the disk (inclination, scale height, dust mass, flaring exponent and surface/volume density exponent) by model fitting to multiwavelength (F606W and F814W) HST observations together with a literature compiled spectral energy distribution. A new tool set was developed for finding optimal fits of MCFOST radiative transfer models using the MCMC code emcee to efficiently explore the high dimensional parameter space. It is able to self-consistently and simultaneously fit a wide variety of observables in order to place constraints on the physical properties of a given disk, while also rigorously assessing the uncertainties in those derived properties. We confirm that ESO H$\alpha$ 569 is an optically thick nearly edge-on protoplanetary disk. The shape of the disk is well described by a flared disk model with an exponentially tapered outer edge, consistent with models previously advocated on theoretical grounds and supported by millimeter interferometry. The scattered light images and spectral energy distribution are best fit by an unusually high total disk mass (gas+dust assuming a ratio of 100:1) with a disk-to-star mass ratio of 0.16.Comment: Accepted for publication in Ap

Opportunities and Challenges of Extracting Values in Autobiographical Narratives

We report three studies in which we applied a value dictionary to narratives. Our objective was to test a theory-driven value dictionary for extracting valuable information from autobiographical and narrative texts. In Studies 1 (N = 106) and 2 (N = 152), participants wrote short autobiographical narratives and in Study 3 (N = 150), participants wrote narratives based on ambiguous stimuli. Participants in all three studies also completed the Portrait Value Questionnaire as a self-report measure of values. Overall, our results demonstrate that it is possible to extract value-relevant information from these narratives. Extracted values from autobiographical narratives showed average correlations of 0.07 (Study 1) and 0.12 (Study 2) with self-reports compared to an average correlation of 0.01 for the extracted values from implicit motive tasks (Study 3). The correlations with self-reports were in line with previous validation studies. The most salient values in narratives diverged somewhat, with a stronger emphasis on achievement values compared to self-reports, probably due to the nature of salient episodes within one's life that require demonstrating success according to social standards. Benevolence values were consistently most important in both self-ratings and text-based scoring. The value structure emerging from narratives diverged from the theoretically predicted structure, yet broad personally vs. socially focused value dimensions were qualitatively discernible. We highlight opportunities and challenges for future value research using autobiographical stories

Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia.

Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased necrotic death of inflammatory cells, thereby resulting in lethal damage to surrounding tissue. Collectively, our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation. This disruption leads to not only increased susceptibility to S. aureus infection, but also extensive lung damage. Importantly, we show that combination treatment of antibiotic and NADPH oxidase inhibitor significantly improved animal survival from coinfection. These findings suggest that treatment strategies that target both bacteria and oxidative stress will significantly benefit patients with influenza-complicated S. aureus pneumonia

Airborne observations of methane emissions from rice cultivation in the Sacramento Valley of California

Airborne measurements of methane (CH4) and carbon dioxide (CO2) were taken over the rice growing region of California's Sacramento Valley in the late spring of 2010 and 2011. From these and ancillary measurements, we show that CH4 mixing ratios were higher in the planetary boundary layer above the Sacramento Valley during the rice growing season than they were before it, which we attribute to emissions from rice paddies. We derive daytime emission fluxes of CH4 between 0.6 and 2.0% of the CO2 taken up by photosynthesis on a per carbon, or mole to mole, basis. We also use a mixing model to determine an average CH 4/CO2 flux ratio of -0.6% for one day early in the growing season of 2010. We conclude the CH4/CO2 flux ratio estimates from a single rice field in a previous study are representative of rice fields in the Sacramento Valley. If generally true, the California Air Resources Board (CARB) greenhouse gas inventory emission rate of 2.7×1010g CH4/yr is approximately three times lower than the range of probable CH4 emissions (7.8-9.3×10 10g CH4/yr) from rice cultivation derived in this study. We attribute this difference to decreased burning of the residual rice crop since 1991, which leads to an increase in CH4 emissions from rice paddies in succeeding years, but which is not accounted for in the CARB inventory. © 2012. American Geophysical Union. All Rights Reserved

Relationships between species richness and biomass production are context dependent in grasslands differing in land-use and seed addition.

Despite evidence from grasslands experiments suggesting that plant species loss reduces biomass production, the strength of biodiversity-ecosystem functioning relationships in managed grasslands is still debated. High land-use intensity and reduced species pools are often suggested to make relationships between biodiversity and productivity less positive or even negative, but concrete evidence is still scarce. We investigated biodiversity-productivity relationships over two years in 150 managed grasslands in Germany. Specifically, we distinguished between relationships of biodiversity and biomass production in managed grasslands (1) varying in land-use intensity (e.g. of mowing, grazing and/or fertilization), (2) where land-use intensity is experimentally reduced, and (3) where additionally to land-use reductions, species pools are enlarged by seed addition. Among grasslands varying in land-use intensity, we found negative biodiversity-productivity relationships. Land-use reduction weakened these relationships, towards neutral, and sometimes, even positive relationships. Seed addition reduced species pool limitations, but this did not strengthen biodiversity-productivity relationships. Our findings indicate that land-use intensity is an important factor explaining the predominantly negative biodiversity-productivity relationships in managed grasslands. While we did not find that species pool limitations weakened biodiversity-productivity relationships, our results are based on a two-year-old experiment, possibly such effects are only visible in the long-term. Ultimately, advancing insights on biodiversity-ecosystem functioning relationships helps us to understand under which conditions agricultural production may benefit from promoting biodiversity

Therapeutic Efficacy of Human Hepatocyte Transplantation in a SCID/uPA Mouse Model with Inducible Liver Disease

Severe Combined Immune Deficient (SCID)/Urokinase-type Plasminogen Activator (uPA) mice undergo liver failure and are useful hosts for the propagation of transplanted human hepatocytes (HH) which must compete with recipient-derived hepatocytes for replacement of the diseased liver parenchyma. While partial replacement by HH has proven useful for studies with Hepatitis C virus, complete replacement of SCID/uPA mouse liver by HH has never been achieved and limits the broader application of these mice for other areas of biomedical research. The herpes simplex virus type-1 thymidine kinase (HSVtk)/ganciclovir (GCV) system is a powerful tool for cell-specific ablation in transgenic animals. The aim of this study was to selectively eliminate murine-derived parenchymal liver cells from humanized SCID/uPA mouse liver in order to achieve mice with completely humanized liver parenchyma. Thus, we reproduced the HSVtk (vTK)/GCV system of hepatic failure in SCID/uPA mice.In vitro experiments demonstrated efficient killing of vTK expressing hepatoma cells after GCV treatment. For in vivo experiments, expression of vTK was targeted to the livers of FVB/N and SCID/uPA mice. Hepatic sensitivity to GCV was first established in FVB/N mice since these mice do not undergo liver failure inherent to SCID/uPA mice. Hepatic vTK expression was found to be an integral component of GCV-induced pathologic and biochemical alterations and caused death due to liver dysfunction in vTK transgenic FVB/N and non-transplanted SCID/uPA mice. In SCID/uPA mice with humanized liver, vTK/GCV caused death despite extensive replacement of the mouse liver parenchyma with HH (ranging from 32-87%). Surprisingly, vTK/GCV-dependent apoptosis and mitochondrial aberrations were also localized to bystander vTK-negative HH.Extensive replacement of mouse liver parenchyma by HH does not provide a secure therapeutic advantage against vTK/GCV-induced cytotoxicity targeted to residual mouse hepatocytes. Functional support by engrafted HH may be secured by strategies aimed at limiting this bystander effect

HST/NICMOS Imaging of Disks and Envelopes Around Very Young Stars

We present HST/NICMOS observations with 0.1" (15 AU) resolution of six young stellar objects in the Taurus star-formation region. The targets of our survey are three Class I IRAS sources (IRAS 04016+2610, IRAS 04248+2612, and IRAS 04302+2247) and three low-luminosity stars (DG Tau B, Haro 6-5B, and CoKu Tau/1) associated with Herbig Haro jets. The broad-band images show that the near-infrared radiation from these sources is dominated by light scattered from dusty circumstellar material distributed in a region 10 - 15 times the size of our solar system. Although the detailed morphologies of the individual objects are unique, the observed young stellar objects share common features. All of the circumstellar reflection nebulae are crossed by dark lanes from 500 - 900 AU in extent and from less than 50 to 350 AU in apparent thickness. The absorption lanes extend perpendicular to known optical and millimeter outflows in these sources. We interpret the dark lanes as optically thick circumstellar disks seen in silhouette against bright reflection nebulosity. The bipolar reflection nebulae extending perpendicular to the dust lanes appear to be produced by scattering from the upper and lower surfaces of the disks and from dusty material within or on the walls of the outflow cavities. Out of five objects in which the central source is directly detected, two are found to be subarcsecond binaries. This mini-survey is the highest resolution near-infrared study to date of circumstellar environments around solar-type stars with age <= 1 Myr.Comment: 34 pages, 4 figures; also available at http://spider.ipac.caltech.edu/staff/brandner/topics/disks/disks.html ; accepted for publication in AJ (March 1999 issue