Transcriptomic Profiles of Monocyte-Derived Macrophages in Response to Escherichia coli is Associated with the Host Genetics.

Reactive Nitrogen Species (RNS) are a group of bactericidal molecules produced by macrophages in response to pathogens in a process called oxidative burst. Nitric oxide (NO-) is a member of RNS produced from arginine by inducible Nitric Oxide Synthase (iNOS) enzyme. The activity of iNOS and production of NO- by macrophages following stimulation is one of the indicators of macrophage polarization towards M1/proinflammatory. Production of NO- by bovine monocyte-derived macrophage (MDM) and mouse peritoneal macrophages has been shown to be strongly associated with host genetic with the heritability of 0.776 in bovine MDM and 0.8 in mouse peritoneal macrophages. However, the mechanism of genetic regulation of macrophage response has remained less explored. In the current study, the transcriptome of bovine MDMs was compared between two extreme phenotypes that had been classified as high and low responder based on NO- production. The results showed that 179 and 392 genes were differentially expressed (DE) between high and low responder groups at 3 and 18 hours after exposure to Escherichia coli, respectively. A set of 11 Transcription Factors (TFs) (STAT1, IRF7, SPI1, STAT4, IRF1, HIF1A, FOXO3, REL, NFAT5, HIC1, and IRF4) at 3 hours and a set of 13 TFs (STAT1, IRF1, HIF1A, STAT4, ATF4, TP63, EGR1, CDKN2A, RBL1, E2F1, PRDM1, GATA3, and IRF4) at 18 hours after exposure to E. coli were identified to be differentially regulated between the high and low responder phenotypes. These TFs were found to be divided into two clusters of inflammatory- and hypoxia-related TFs. Functional analysis revealed that some key canonical pathways such as phagocytosis, chemotaxis, antigen presentation, and cell-to-cell signalling are enriched among the over-expressed genes by high responder phenotype. Based on the results of this study, it was inferred that the functional characteristics of bovine MDMs are associated with NO-based classification. Since NO- production is strongly associated with host genetics, this study for the first time shows the distinct proinflammatory profiles of macrophages are controlled by the natural genetic polymorphism in an outbred population. In addition, the results suggest that genetics can be considered as a new dimension in the current model of macrophage polarization which is currently described by the combination of stimulants, only

Modeling natural emissions in the Community Multiscale Air Quality (CMAQ) model – Part 2: Modifications for simulating natural emissions

The Community Multiscale Air Quality (CMAQ) model version 4.6 has been revised with regard to the representation of chlorine (HCl, ClNO<sub>2</sub>) and sulfur (dimethylsulfide, or DMS, and H<sub>2</sub>S), and evaluated against observations and earlier published models. Chemistry parameterizations were based on published reaction kinetic data and a recently developed cloud chemistry model that includes heterogeneous reactions of organic sulfur compounds. Evaluation of the revised model was conducted using a recently enhanced data base of natural emissions that includes ocean and continental sources of DMS, H<sub>2</sub>S, chlorinated gases and lightning NO<sub>x</sub> for the continental United States and surrounding regions. Results using 2002 meteorology and emissions indicated that most simulated "natural" (plus background) chemical and aerosol species exhibit the expected seasonal variations at the surface. Ozone exhibits a winter and early spring maximum consistent with ozone data and an earlier published model. Ozone distributions reflect the influences of atmospheric dynamics and pollutant background levels imposed on the CMAQ simulation by boundary conditions derived from a global model. A series of model experiments reveals that the consideration of gas-phase organic sulfur chemistry leads to sulfate aerosol increases over most of the continental United States. Cloud chemistry parameterization changes result in widespread decreases in SO<sub>2</sub> across the modeling domain and both increases and decreases in sulfate. Most cloud-mediated sulfate increases occurred mainly over the Pacific Ocean (up to about 0.1 μg m<sup>−3</sup>) but also over and downwind from the Gulf of Mexico (including parts of the eastern US). Geographic variations in simulated SO<sub>2</sub> and sulfate are due to the link between DMS/H<sub>2</sub>S and their byproduct SO<sub>2</sub>, the heterogeneity of cloud cover and precipitation (precipitating clouds act as net sinks for SO<sub>2</sub> and sulfate), and the persistence of cloud cover (the largest relative sulfate increases occurred over the persistently cloudy Gulf of Mexico and western Atlantic Ocean). Overall, the addition of organic sulfur chemistry increased hourly surface sulfate levels by up to 1–2 μg m<sup>−3</sup> but reduced sulfate levels in the vicinity of high SO<sub>2</sub> emissions (e.g., wildfires). Simulated surface levels of DMS compare reasonably well with observations in the marine boundary layer where DMS oxidation product levels are lower than observed. This implies either a low bias in model oxidation rates of organic sulfur species or a low bias in the boundary conditions for DMS oxidation products. This revised version of CMAQ provides a tool for realistically simulating the influence of natural emissions on air quality

Daybreak. Scena for Voice with Pianoforte or Orchestra Accompaniment

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Trabecular microarchitecture in established osteoporosis: relationship between vertebrae, distal radius and calcaneus by X-ray imaging texture analysis

INTRODUCTION: Osteoporosis is an alteration of bone mass and microarchitecture leading to an increased risk of fractures. A radiograph is a 2D projection of the 3D bone network exposing a texture, that can be assessed by texture analysis. We compared the trabecular microarchitecture of the spine, radius and calcaneus in a series of osteoporotic cadavers. MATERIALS AND METHODS: Thirty-four cadavers (11 men, 23 women), mean age 85.2±2.1years, were radiographed from T4 to L5 to identify those with vertebral fractures (FV). Non-fractured vertebrae (NFV), radius and calcaneus were taken and analyzed by densitometry, radiography and texture analysis under run-length, skeletonization of the trabeculae, and fractal geometry. RESULTS: Six subjects (five women, one man) were selected, mean age 82.5±5.5years. Twelve calcanei and 10 radii were taken. Two radii were excluded. The texture of NFV was significantly correlated (P<0.01) with that of the radius for horizontal run-lengths. No relationship between the texture of NFV and calcaneus was found. DISCUSSION: In the horizontal direction (perpendicular to the stress lines), the microarchitecture of NFV and radius showed a disappearance of the transverse rods anchoring the plates. Due to its particular microarchitecture, the calcaneus is not representative of the vertebral status. CONCLUSION: Bone densitometry provides no information about microarchitecture. Texture analysis of X-ray images of the radius would be a minimally invasive tool, providing an early detection of microarchitectural alterations. LEVEL OF EVIDENCE: IV retrospective study

Reverse wedge osteotomy of the distal radius in Madelung's deformity

Madelung\u27s deformity results from a growth defect in the palmar and ulnar region of the distal radius. It presents as an excessively inclined radial joint surface, inducing "spontaneous progressive palmar subluxation of the wrist". The principle of reverse wedge osteotomy (RWO) consists in the reorientation of the radial joint surface by taking a circumferential bone wedge, the base of which is harvested from the excess of the radial and dorsal cortical bone of the distal radius, then turning it over and putting back this reverse wedge into the osteotomy so as to obtain closure on the excess and opening on the deficient cortical bone. RWO corrects the palmar subluxation of the carpus and improves distal radio-ulnar alignment. All five bilaterally operated patients were satisfied, esthetically and functionally. Its corrective power gives RWO a place apart among the surgical techniques currently available in Madelung\u27s deformity

The effect of interpolation methods in temperature and salinity trends in the Western Mediterranean

Temperature and salinity data in the historical record are scarce and unevenly distributed in space and time and the estimation of linear trends is sensitive to different factors. In the case of the Western Mediterranean, previous works have studied the sensitivity of these trends to the use of bathythermograph data, the averaging methods or the way in which gaps in time series are dealt with. In this work, a new factor is analysed: the effect of data interpolation. Temperature and salinity time series are generated averaging existing data over certain geographical areas and also by means of interpolation. Linear trends from both types of time series are compared. There are some differences between both estimations for some layers and geographical areas, while in other cases the results are consistent. Those results which do not depend on the use of interpolated or non-interpolated data, neither are influenced by data analysis methods can be considered as robust ones. Those results influenced by the interpolation process or the factors analysed in previous sensitivity tests are not considered as robust results

Inference by belief propagation in composite systems

We devise a message passing algorithm for probabilistic inference in composite systems, consisting of a large number of variables, that exhibit weak random interactions among all variables and strong interactions with a small subset of randomly chosen variables; the relative strength of the two interactions is controlled by a free parameter. We examine the performance of the algorithm numerically on a number of systems of this type for varying mixing parameter values

A simple genetic basis of adaptation to a novel thermal environment results in complex metabolic rewiring in Drosophila

BACKGROUND:Population genetic theory predicts that rapid adaptation is largely driven by complex traits encoded by many loci of small effect. Because large-effect loci are quickly fixed in natural populations, they should not contribute much to rapid adaptation. RESULTS:To investigate the genetic architecture of thermal adaptation - a highly complex trait - we performed experimental evolution on a natural Drosophila simulans population. Transcriptome and respiration measurements reveal extensive metabolic rewiring after only approximately 60 generations in a hot environment. Analysis of genome-wide polymorphisms identifies two interacting selection targets, Sestrin and SNF4Aγ, pointing to AMPK, a central metabolic switch, as a key factor for thermal adaptation. CONCLUSIONS:Our results demonstrate that large-effect loci segregating at intermediate allele frequencies can allow natural populations to rapidly respond to selection. Because SNF4Aγ also exhibits clinal variation in various Drosophila species, we suggest that this large-effect polymorphism is maintained by temporal and spatial temperature variation in natural environments.François Mallard, Viola Nolte, Ray Tobler, Martin Kapun and Christian Schlöttere

Spontaneous Transition of Turbulent Flames to Detonations in Unconfined Media

Deflagration-to-detonation transition (DDT) can occur in environments ranging from experimental and industrial systems to astrophysical thermonuclear (type Ia) supernovae explosions. Substantial progress has been made in explaining the nature of DDT in confined systems with walls, internal obstacles, or pre-existing shocks. It remains unclear, however, whether DDT can occur in unconfined media. Here we use direct numerical simulations (DNS) to show that for high enough turbulent intensities unconfined, subsonic, premixed, turbulent flames are inherently unstable to DDT. The associated mechanism, based on the nonsteady evolution of flames faster than the Chapman-Jouguet deflagrations, is qualitatively different from the traditionally suggested spontaneous reaction wave model, and thus does not require the formation of distributed flames. Critical turbulent flame speeds, predicted by this mechanism for the onset of DDT, are in agreement with DNS results.Comment: 4 pages, 3 figures; accepted to Physical Review Letter