The hypoxic tissue microenvironment as a driver of mucosal inflammatory resolution

On the backdrop of all acute inflammatory processes lies the activation of the resolution response. Recent years have witnessed an emerging interest in defining molecular factors that influence the resolution of inflammation. A keystone feature of the mucosal inflammatory microenvironment is hypoxia. The gastrointestinal tract, particularly the colon, exists in a state of physiological hypoxia and during active inflammation, this hypoxic state is enhanced as a result of infiltrating leukocyte oxygen consumption and the activation of oxygen consuming enzymes. Most evidence suggests that mucosal hypoxia promotes the active resolution of inflammation through a variety of mechanisms, including extracellular acidification, purine biosynthesis/salvage, the generation of specialized pro-resolving lipid mediators (ie. resolvins) and altered chemokine/cytokine expression. It is now appreciated that infiltrating innate immune cells (neutrophils, eosinophils, macrophages) have an important role in molding the tissue microenvironment to program an active resolution response. Structural or functional dysregulation of this inflammatory microenvironment can result in the loss of tissue homeostasis and ultimately progression toward chronicity. In this review, we will discuss how inflammatory hypoxia drives mucosal inflammatory resolution and its impact on other microenvironmental factors that influence resolution

Topo-edaphic controls over woody plant biomass in South African savannas

The distribution of woody biomass in savannas reflects spatial patterns fundamental to ecosystem processes, such as water flow, competition, and herbivory, and is a key contributor to savanna ecosystem services, such as fuelwood supply. While total precipitation sets an upper bound on savanna woody biomass, the extent to which substrate and terrain constrain trees and shrubs below this maximum remains poorly understood, often occluded by local-scale disturbances such as fire and trampling. Here we investigate the role of hillslope topography and soil properties in controlling woody plant aboveground biomass (AGB) in Kruger National Park, South Africa. Large-area sampling with airborne Light Detection and Ranging (LiDAR) provided a means to average across local-scale disturbances, revealing an unexpectedly linear relationship between AGB and hillslope-position on basalts, where biomass levels were lowest on crests, and linearly increased toward streams (<i>R</i><sup>2</sup> = 0.91). The observed pattern was different on granite substrates, where AGB exhibited a strongly non-linear relationship with hillslope position: AGB was high on crests, decreased midslope, and then increased near stream channels (<i>R</i><sup>2</sup> = 0.87). Overall, we observed 5-to-8-fold lower AGB on clayey, basalt-derived soil than on granites, and we suggest this is due to herbivore-fire interactions rather than lower hydraulic conductivity or clay shrinkage/swelling, as previously hypothesized. By mapping AGB within and outside fire and herbivore exclosures, we found that basalt-derived soils support tenfold higher AGB in the absence of fire and herbivory, suggesting high clay content alone is not a proximal limitation on AGB. Understanding how fire and herbivory contribute to AGB heterogeneity is critical to predicting future savanna carbon storage under a changing climate

Detrital Zircon Record of Magmatism and Sediment Dispersal Across the North American Cordilleran Arc System (28–48°N)

As zircon U-Pb geochronology has become a leading method in sediment provenance studies and basin analysis over the past 20 years, the volume of detrital zircon data made available in published literature has enabled researchers to go beyond source-to-sink provenance studies to explore increasingly complex geologic problems. In this review, we utilize the growing body of detrital zircon data acquired from Jurassic-Paleocene forearc and foreland basin strata of the North American Cordillera to investigate the Mesozoic to earliest Cenozoic evolution of the arc and its associated basins between 28°N and 48°N. Our compilation includes 830 detrital zircon samples (101,898 individual ages) from 70 studies published between 2000 and 2020. For comparative purposes, we also compile 1307 igneous zircon U-Pb ages that characterize the magmatic history of the arc. We place primary emphasis on detrital zircon ages between 251 and 56 Ma that we infer to be uniquely derived from magmatic sources in the arc. Informed by existing knowledge of magmatic, structural, and sedimentological processes that acted on the orogen, we investigate spatial and temporal trends in these “arc-derived zircon” to establish a detrital record of arc magmatism, investigate source-to-sink relationships between the arc and adjacent basins, and discuss controls on sediment dispersal across the orogen. Our review shows that compilations of detrital zircon data from the Cordilleran forearc and foreland basin systems are excellent proxies for arc magmatism because the basins are enriched in arc-derived zircon and compilations provide space- and time-integrated records of crystallization ages. The compiled detrital zircon data support a history of continuous arc magmatism throughout Mesozoic and earliest Cenozoic time, characterized by low-volume magmatism from Triassic-Early Jurassic time (~251–174 Ma) and episodic higher-volume magmatism from Middle Jurassic-Late Cretaceous time (~174–66 Ma). These trends elucidate the initiation and timing of magmatic events at the orogen-scale and corroborate our understanding of cyclic arc behavior. Detrital zircon distributions are spatially and temporally variable both within and across basins, which we discuss relative to topographic development of the orogen and attendant responses of sediment dispersal systems. Detrital zircon distributions in the forearc signal rapid transfer of sediment from the arc to basins dominantly via fluvial processes. In contrast, detrital zircon distributions across the foreland reflect the presence of topographic barriers in the hinterland region of the arc that effectively isolated parts of the foreland. The presence of hinterland topography in turn highlights the important role of ash-fall events in delivering arc-derived zircon to the foreland, underscoring the need to consider ash-fall processes in paleodrainage reconstructions. These broad regional trends, and in general the close linkage between orogenic process and sediment dispersal, emerge from our compilation because it averages out much of the local variability observed in studies of more limited geographic or temporal extent

Separation and identification of dominant mechanisms in double photoionization

Double photoionization by a single photon is often discussed in terms of two contributing mechanisms, {\it knock-out} (two-step-one) and {\it shake-off} with the latter being a pure quantum effect. It is shown that a quasi-classical description of knock-out and a simple quantum calculation of shake-off provides a clear separation of the mechanisms and facilitates their calculation considerably. The relevance of each mechanism at different photon energies is quantified for helium. Photoionization ratios, integral and singly differential cross sections obtained by us are in excellent agreement with benchmark experimental data and recent theoretical results.Comment: 4 pages, 5 figure

Duplex ultrasound in aneurysm surveillance following endovascular aneurysm repair: a comparison with computed tomography aortography

ObjectivesCumulative radiation dose, cost, and increased demand for computed tomography aortography (CTA) suggest that duplex ultrasonography (DU) may be an alternative to CTA-based surveillance. We compared CTA with DU during endovascular aneurysm repair (EVAR) follow-up.MethodsPatients undergoing EVAR had clinical and radiological follow-up data entered in a prospectively maintained database. For the purpose of this study, the gold standard test for endoleak detection was CTA, and an endoleak detected on DU alone was assumed to be a false positive result. DU interpretation was performed independently of CTA and vice versa.ResultsOne hundred thirty-two patients underwent EVAR, of whom 117 attended for follow-up ranging from six months to nine years (mean, 32 months). Adequate aneurysm sac visualisation on DU was not possible in 1.7% of patients, predominantly due to obesity. Twenty-eight endoleaks were detected in 28 patients during follow-up. Of these, 24 were initially identified on DU (four false negative DU examinations), and eight had at least one negative CTA with a positive DU prior to diagnosis. Twenty-three endoleaks were type II in nature and three of these patients had increased sac size. There was one type I and four type III endoleaks. Two of these (both type III) had an increased sac size. Of 12 patients with increased aneurysm size of 5 mm or more at follow-up, five had an endoleak visible on DU, yet negative CTA and a further five had endoleak visualisation on both DU and CTA. Of six endoleaks which underwent re-intervention, all were initially picked up on DU. One of these endoleaks was never demonstrated on CTA and a further two had at least one negative CTA prior to endoleak confirmation. Positive predictive value for DU was 45% and negative predictive value 94%. Specificity of DU for endoleak detection was 67% when compared with CTA, because of the large number of false positive DU results. Sensitivity for DU was 86%, with all clinically significant endoleaks demonstrated on CTA also detected on DU.ConclusionDespite its low positive predictive value, we found DU to be a sensitive test for the detection of clinically significant endoleaks. Given concerns about cumulative radiation exposure and cost, and the surprisingly low sensitivity of CTA for endoleak detection in this series, selective CTA based on DU surveillance may be a more appropriate long-term strategy

Spitzer IRS Observations of the Galactic Center: Shocked Gas in the Radio Arc Bubble

We present Spitzer IRS spectra (R ~600, 10 - 38 micron) of 38 positions in the Galactic Center (GC), all at the same Galactic longitude and spanning plus/minus 0.3 degrees in latitude. Our positions include the Arches Cluster, the Arched Filaments, regions near the Quintuplet Cluster, the ``Bubble'' lying along the same line-of-sight as the molecular cloud G0.11-0.11, and the diffuse interstellar gas along the line-of-sight at higher Galactic latitudes. From measurements of the [O IV], [Ne II], [Ne III], [Si II], [S III], [S IV], [Fe II], [Fe III], and H_2 S(0), S(1), and S(2) lines we determine the gas excitation and ionic abundance ratios. The Ne/H and S/H abundance ratios are ~ 1.6 times that of the Orion Nebula. The main source of excitation is photoionization, with the Arches Cluster ionizing the Arched Filaments and the Quintuplet Cluster ionizing the gas nearby and at lower Galactic latitudes including the far side of the Bubble. In addition, strong shocks ionize gas to O^{+3} and destroy dust grains, releasing iron into the gas phase (Fe/H ~ 1.3 times 10^{-6} in the Arched Filaments and Fe/H ~ 8.8 times 10^{-6} in the Bubble). The shock effects are particularly noticeable in the center of the Bubble, but O$^{+3}$ is present in all positions. We suggest that the shocks are due to the winds from the Quintuplet Cluster Wolf-Rayet stars. On the other hand, the H_2 line ratios can be explained with multi-component models of warm molecular gas in photodissociation regions without the need for H_2 production in shocks.Comment: 51 pages, 17 figures To be published in the Astrophysical Journa

Antiadhesive Role of Apical Decay-accelerating Factor (CD55) in Human Neutrophil Transmigration across Mucosal Epithelia

Neutrophil migration across mucosal epithelium during inflammatory episodes involves the precise orchestration of a number a cell surface molecules and signaling pathways. After successful migration to the apical epithelial surface, apically localized epithelial proteins may serve to retain PMN at the lumenal surface. At present, identification of apical epithelial ligands and their PMN counter-receptors remain elusive. Therefore, to define the existence of apical epithelial cell surface proteins involved in PMN–epithelial interactions, we screened a panel of antibodies directed against epithelial plasma membranes. This strategy identified one antibody (OE-1) that both localized to the apical cell membrane and significantly inhibited PMN transmigration across epithelial monolayers. Microsequence analysis revealed that OE-1 recognized human decay-accelerating factor (DAF, CD55). DAF is a highly glycosylated, 70–80-kD, glycosyl-phosphatidyinositol–linked protein that functions predominantly as an inhibitor of autologous complement lysis. DAF suppression experiments using antisense oligonucleotides or RNA interference revealed that DAF may function as an antiadhesive molecule promoting the release of PMN from the lumenal surface after transmigration. Similarly, peptides corresponding to the antigen recognition domain of OE-1 resulted in accumulation of PMN on the apical epithelial surface. The elucidation of DAF as an apical epithelial ligand for PMN provides a target for novel anti-inflammatory therapies directed at quelling unwanted inflammatory episodes

Photoelectron Angular Distributions for Two-photon Ionization of Helium by Ultrashort Extreme Ultraviolet Free Electron Laser Pulses

Phase-shift differences and amplitude ratios of the outgoing $s$ and $d$ continuum wave packets generated by two-photon ionization of helium atoms are determined from the photoelectron angular distributions obtained using velocity map imaging. Helium atoms are ionized with ultrashort extreme-ultraviolet free-electron laser pulses with a photon energy of 20.3, 21.3, 23.0, and 24.3 eV, produced by the SPring-8 Compact SASE Source test accelerator. The measured values of the phase-shift differences are distinct from scattering phase-shift differences when the photon energy is tuned to an excited level or Rydberg manifold. The difference stems from the competition between resonant and non-resonant paths in two-photon ionization by ultrashort pulses. Since the competition can be controlled in principle by the pulse shape, the present results illustrate a new way to tailor the continuum wave packet.Comment: 5 pages, 1 table, 3 figure