IL-17 can be protective or deleterious in murine pneumococcal pneumonia

Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains

Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.

Acetaminophen (APAP)-induced liver injury is clinically significant, and APAP overdose in mice often serves as a model for drug-induced liver injury in humans. By specifying that APAP metabolism, reactive metabolite formation, glutathione depletion, and mitigation of mitochondrial damage within individual hepatocytes are functions of intralobular location, an earlier virtual model mechanism provided the first concrete multiattribute explanation for how and why early necrosis occurs close to the central vein (CV). However, two characteristic features could not be simulated consistently: necrosis occurring first adjacent to the CV, and subsequent necrosis occurring primarily adjacent to hepatocytes that have already initiated necrosis. We sought parsimonious model mechanism enhancements that would manage spatiotemporal heterogeneity sufficiently to enable meeting two new target attributes and conducted virtual experiments to explore different ideas for model mechanism improvement at intrahepatocyte and multihepatocyte levels. For the latter, evidence supports intercellular communication via exosomes, gap junctions, and connexin hemichannels playing essential roles in the toxic effects of chemicals, including facilitating or counteracting cell death processes. Logic requiring hepatocytes to obtain current information about whether downstream and lateral neighbors have triggered necrosis enabled virtual hepatocytes to achieve both new target attributes. A virtual hepatocyte that is glutathione-depleted uses that information to determine if it will initiate necrosis. When a less-stressed hepatocyte is flanked by at least two neighbors that have triggered necrosis, it too will initiate necrosis. We hypothesize that the resulting intercellular communication-enabled model mechanism is analogous to the actual explanation for APAP-induced hepatotoxicity at comparable levels of granularity

In Vivo Ultrasonic Detection of Polyurea Crosslinked Silica Aerogel Implants

Background:Polyurea crosslinked silica aerogels are highly porous, lightweight, and mechanically strong materials with great potential for in vivo applications. Recent in vivo and in vitro studies have demonstrated the biocompatibility of this type of aerogel. the highly porous nature of aerogels allows for exceptional thermal, electric, and acoustic insulating capabilities that can be taken advantage of for non-invasive external imaging techniques. Sound-based detection of implants is a low cost, non-invasive, portable, and rapid technique that is routinely used and readily available in major clinics and hospitals.Methodology:In this study the first in vivo ultrasound response of polyurea crosslinked silica aerogel implants was investigated by means of a GE Medical Systems LogiQe diagnostic ultrasound machine with a linear array probe. Aerogel samples were inserted subcutaneously and sub-muscularly in a) fresh animal model and b) cadaveric human model for analysis. For comparison, samples of polydimethylsiloxane (PDMS) were also imaged under similar conditions as the aerogel samples.Conclusion/significance:Polyurea crosslinked silica aerogel (X-Si aerogel) implants were easily identified when inserted in either of the regions in both fresh animal model and cadaveric model. the implant dimensions inferred from the images matched the actual size of the implants and no apparent damage was sustained by the X-Si aerogel implants as a result of the ultrasonic imaging process. the aerogel implants demonstrated hyperechoic behavior and significant posterior shadowing. Results obtained were compared with images acquired from the PDMS implants inserted at the same location

Experienced migratory songbirds do not display goal-ward orientation after release following a cross-continental displacement: an automated telemetry study

The ability to navigate implies that animals have the capability to compensate for geographical displacement and return to their initial goal or target. Although some species are capable of adjusting their direction after displacement, the environmental cues used to achieve this remain elusive. Two possible cues are geomagnetic parameters (magnetic map hypothesis) or atmospheric odour-forming gradients (olfactory map hypothesis). In this study, we examined both of these hypotheses by surgically deactivating either the magnetic or olfactory sensory systems in experienced white-throated sparrows (Zonotrichia albicollis) captured in southern Ontario, Canada, during spring migration. Treated, sham-treated, and intact birds were then displaced 2,200 km west to Saskatchewan, Canada. Tracking their initial post-displacement migration using an array of automated VHF receiving towers, we found no evidence in any of the groups for compensatory directional response towards their expected breeding grounds. Our results suggest that white-throated sparrows may fall back to a simple constant-vector orientation strategy instead of performing true navigation after they have been geographically displaced to an unfamiliar area during spring migration. Such a basic strategy may be more common than currently thought in experienced migratory birds and its occurrence could be determined by habitat preferences or range size

Sewage reflects the microbiomes of human populations

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in mBio 6 (2015): e02574-14, doi:10.1128/mBio.02574-14.Molecular characterizations of the gut microbiome from individual human stool samples have identified community patterns that correlate with age, disease, diet, and other human characteristics, but resources for marker gene studies that consider microbiome trends among human populations scale with the number of individuals sampled from each population. As an alternative strategy for sampling populations, we examined whether sewage accurately reflects the microbial community of a mixture of stool samples. We used oligotyping of high-throughput 16S rRNA gene sequence data to compare the bacterial distribution in a stool data set to a sewage influent data set from 71 U.S. cities. On average, only 15% of sewage sample sequence reads were attributed to human fecal origin, but sewage recaptured most (97%) human fecal oligotypes. The most common oligotypes in stool matched the most common and abundant in sewage. After informatically separating sequences of human fecal origin, sewage samples exhibited ~3× greater diversity than stool samples. Comparisons among municipal sewage communities revealed the ubiquitous and abundant occurrence of 27 human fecal oligotypes, representing an apparent core set of organisms in U.S. populations. The fecal community variability among U.S. populations was significantly lower than among individuals. It clustered into three primary community structures distinguished by oligotypes from either: Bacteroidaceae, Prevotellaceae, or Lachnospiraceae/Ruminococcaceae. These distribution patterns reflected human population variation and predicted whether samples represented lean or obese populations with 81 to 89% accuracy. Our findings demonstrate that sewage represents the fecal microbial community of human populations and captures population-level traits of the human microbiome.Funding for this work was provided by the NIH grant R01AI091829-01A1 to S.L.M. and M.L.S

Injury and performance related biomechanical differences between recreational and collegiate runners

IntroductionRunning related injuries (RRI) are common, but factors contributing to running performance and RRIs are not commonly compared between different types of runners.MethodsWe compared running biomechanics previously linked to RRIs and performance between 27 recreational and 35 collegiate runners. Participants completed 5 overground running trials with their dominant limb striking a force plate, while outfitted with standardised footwear and 3-dimensional motion capture markers.ResultsPost hoc comparisons revealed recreational runners had a larger vertical loading rate (194.5 vs. 111.5 BW/s, p < 0.001) and shank angle (6.80 vs. 2.09, p < 0.001) compared with the collegiate runners who demonstrated greater vertical impulse (0.349 vs. 0.233 BWs, p < 0.001), negative impulse (−0.022 vs. −0.013 BWs, p < 0.001), positive impulse (0.024 vs. 0.014 BWs, p < 0.001), and propulsive force (0.390 vs. 0.333 BW, p = 0.002). Adjusted for speed, collegiate runners demonstrated greater total support moment (TSM), plantar flexor moment, knee extensor moment, hip extensor moment, and had greater proportional plantar flexor moment contribution and less knee extensor moment contribution to the TSM compared with recreational runners. Unadjusted for speed, collegiate runners compared with recreational had greater TSM and plantar flexor moment but similar joint contributions to the TSM.DiscussionGreater ankle joint contribution may be more efficient and allow for greater capacity to increase speed. Improving plantarflexor function during running provides a strategy to improve running speed among recreational runners. Moreover, differences in joint kinetics and ground reaction force characteristics suggests that recreational and collegiate runners may experience different types of RRI

Suppressed Magnetization at the Surfaces and Interfaces of Ferromagnetic Metallic Manganites

What happens to ferromagnetism at the surfaces and interfaces of manganites? With the competition between charge, spin, and orbital degrees of freedom, it is not surprising that the surface behavior may be profoundly different than that of the bulk. Using a powerful combination of two surface probes, tunneling and polarized x-ray interactions, this paper reviews our work on the nature of the electronic and magnetic states at manganite surfaces and interfaces. The general observation is that ferromagnetism is not the lowest energy state at the surface or interface, which results in a suppression or even loss of ferromagnetic order at the surface. Two cases will be discussed ranging from the surface of the quasi-2D bilayer manganite (La$_{2-2x}$Sr$_{1+2x}$Mn$_2$O$_7$) to the 3D Perovskite (La$_{2/3}$Sr$_{1/3}$MnO$_3$)/SrTiO$_3$ interface. For the bilayer manganite, that is, ferromagnetic and conducting in the bulk, these probes present clear evidence for an intrinsic insulating non-ferromagnetic surface layer atop adjacent subsurface layers that display the full bulk magnetization. This abrupt intrinsic magnetic interface is attributed to the weak inter-bilayer coupling native to these quasi-two-dimensional materials. This is in marked contrast to the non-layered manganite system (La$_{2/3}$Sr$_{1/3}$MnO$_3$/SrTiO$_3$), whose magnetization near the interface is less than half the bulk value at low temperatures and decreases with increasing temperature at a faster rate than the bulk.Comment: 15 pages, 13 figure

Distributed deformation ahead of the Cocos-Nazca Rift at the Galapagos triple junction

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 12 (2011): Q11003, doi:10.1029/2011GC003689.The Galapagos triple junction is not a simple ridge-ridge-ridge (RRR) triple junction. The Cocos-Nazca Rift (C-N Rift) tip does not meet the East Pacific Rise (EPR). Instead, two secondary rifts form the link: Incipient Rift at 2°40′N and Dietz Deep volcanic ridge, the southern boundary of the Galapagos microplate (GMP), at 1°10′N. Recently collected bathymetry data are used to investigate the regional tectonics prior to the establishment of the GMP (∼1.5 Ma). South of C-N Rift a band of northeast-trending cracks cuts EPR-generated abyssal hills. It is a mirror image of a band of cracks previously identified north of C-N Rift on the same age crust. In both areas, the western ends of the cracks terminate against intact abyssal hills suggesting that each crack initiated at the EPR spreading center and cut eastward into pre-existing topography. Each crack formed a short-lived triple junction until it was abandoned and a new crack and triple junction initiated nearby. Between 2.5 and 1.5 Ma, the pattern of cracking is remarkably symmetric about C-N Rift providing support for a crack interaction model in which crack initiation at the EPR axis is controlled by stresses associated with the tip of the westward-propagating C-N Rift. The model also shows that offsets of the EPR axis may explain times when cracking is not symmetric. South of C-N Rift, cracks are observed on seafloor as old as 10.5 Ma suggesting that this triple junction has not been a simple RRR triple junction during that time.HS was supported by the U.S. National Science Foundation (NSF) grant OCE‐0751831, DS by NSF grant OCE‐1028537, WZ by NSF grant EAR‐1056317, and LM by NSF grant EAR‐0911151.2012-05-0