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

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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

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