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Human sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed on subsets of immune cells. Siglec-8 is an immune inhibitory Siglec on eosinophils and mast cells, which are effectors in allergic disorders including eosinophilic esophagitis. Inhibition occurs when Siglec-8 is crosslinked by multivalent Siglec ligands in target tissues. Previously we discovered a high-affinity Siglec-8 sialoglycan ligand on human airways composed of terminally sialylated keratan sulfate chains carried on a single protein, DMBT1. Here we extend that approach to another allergic inflammatory target tissue, human esophagus. Lectin overlay histochemistry revealed that Siglec-8 ligands are expressed predominantly by esophageal submucosal glands, and are densely packed in submucosal ducts leading to the lumen. Expression is tissue-specific; esophageal glands express Siglec-8 ligand whereas nearby gastric glands do not. Extraction and resolution by gel electrophoresis revealed a single predominant human esophageal Siglec-8 ligand migrating at >2 MDa. Purification by size exclusion and affinity chromatography, followed by proteomic mass spectrometry, revealed the protein carrier to be MUC5B. Whereas all human esophageal submucosal cells express MUC5B, only a portion convert it to Siglec-8 ligand by adding terminally sialylated keratan sulfate chains. We refer to this as MUC5B S8L. Material from the esophageal lumen of live subjects revealed MUC5B S8L species ranging from ~1–4 MDa. We conclude that MUC5B in the human esophagus is a protein canvas on which Siglec-8 binding sialylated keratan sulfate chains are post-translationally added. These data expand understanding of Siglec-8 ligands and may help us understand their roles in allergic immune regulation. [ABSTRACT FROM AUTHOR]

The origins and evolution of the eosinophilic leukocyte have received only scattered attention since Paul Ehrlich first named this granulocyte. Studies suggest that myeloperoxidase, expressed by granulocytes, and eosinophil peroxidase diverged some 60 to 70 million years ago, but invertebrate to vertebrate evolution of the eosinophil lineage is unknown. Vertebrate eosinophils have been characterized extensively in representative species at light microscopic, ultrastructural, genetic, and biochemical levels. Understanding of eosinophil function continues to expand and includes to date regulation of "Local Immunity And/Or Remodeling/Repair" (the so-called LIAR hypothesis), modulation of innate and adaptive immune responses, maintenance of tissue and metabolic homeostasis, and, under pathologic conditions, inducers of tissue damage, repair, remodeling, and fibrosis. This contrasts with their classically considered primary roles in host defense against parasites and other pathogens, as well as involvement in T-helper 2 inflammatory and immune responses. The eosinophils' early appearance during evolution and continued retention within the innate immune system across taxa illustrate their importance during evolutionary biology. However, successful pregnancies in eosinophil-depleted humans/primates treated with biologics, host immune responses to parasites in eosinophil-deficient mice, and the absence of significant developmental or functional abnormalities in eosinophil-deficient mouse strains under laboratory conditions raise questions of the continuing selective advantages of the eosinophil lineage in mammals and humans. The objectives of this review are to provide an overview on evolutionary origins of eosinophils across the animal kingdom, discuss some of their main functions in the context of potential evolutionary relevance, and highlight the need for further research on eosinophil functions and functional evolution. [ABSTRACT FROM AUTHOR]

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies. [ABSTRACT FROM AUTHOR]

Rationale: The resolution of inflammation is an active process coordinated by mediators and immune cells to restore tissue homeostasis. However, the mechanisms for resolving eosinophilic allergic lung inflammation triggered by inhaled allergens have not been fully elucidated. Objectives: Our objectives were to investigate the cellular mechanism of tissue-resident macrophages involved in the resolution process of eosinophilic lung inflammation. Methods: For the study, we used the institutional review board–approved protocol for human subsegmental bronchoprovocation with allergen, mouse models for allergic lung inflammation, and novel transgenic mice, including a conditional CCL26 knockout. The samples were analyzed using mass cytometry, single-cell RNA sequencing, and biophysical and immunological analyses. Measurements and Main Results: We compared alveolar macrophage (AM) subsets in the BAL before and after allergen provocation. In response to provocation with inhaled allergens, the subsets of AMs are dynamically changed in humans and mice. In the steady state, the AM subset expressing CX3CR1 is a relatively small fraction in bronchoalveolar space and lung tissue but drastically increases after allergen challenges. This subset presents unique patterns of gene expression compared with classical AMs, expressing high C1q family genes. CX3CR1+ macrophages are activated by airway epithelial cell–derived CCL26 via a receptor–ligand interaction. The binding of CCL26 to the CX3CR1+ receptor induces CX3CR1+ macrophages to secrete C1q, subsequently facilitating the clearance of eosinophils. Furthermore, the depletion of CX3CR1 macrophages or CCL26 in airway epithelial cells delays the resolution of allergic lung inflammation displaying prolonged tissue eosinophilia. Conclusions: These findings indicate that the CCL26–CX3CR1 pathway is pivotal in resolving eosinophilic allergic lung inflammation. [ABSTRACT FROM AUTHOR]

Sea ice leads, or fractures account for a small proportion of the Arctic Ocean surface area, but play a critical role in the energy and moisture exchanges between the ocean and atmosphere. As the sea ice area and volume in the Arctic has declined over the past few decades, changes in sea ice leads have not been studied as extensively. A recently developed approach uses artificial intelligence (AI) and satellite thermal infrared window data to build a twenty-year archive of sea ice lead detects with Moderate Resolution Imaging Spectroradiometer (MODIS) and later, an archive from Visible Infrared Imaging Radiometer Suite (VIIRS). The results are now available and show significant improvement over previously published methods. The AI method results have higher detection rates and a high level detection agreement between MODIS and VIIRS. Analysis over the winter season from 2002–2003 through to the 2021–2022 archive reveals lead detections have a small decreasing trend in lead area that can be attributed to increasing cloud cover in the Arctic. This work reveals that leads are becoming increasingly difficult to detect rather than less likely to occur. Although the trend is small and on the same order of magnitude as the uncertainty, leads are likely increasing at a rate of 3700 km2 per year with a range of uncertainty of 3500 km2 after the impact of cloud cover changes are removed. [ABSTRACT FROM AUTHOR]

The Interferometric Monitor for Greenhouse Gases (IMG) operated aboard the polar-orbiting Advanced Earth Observing Satellite from October 1996 through June 1997. The IMG measured upwelling infrared radiance at fine spectral resolution. This paper identifies previously undocumented issues with IMG interferograms and describes procedures for correcting the majority of the affected data. In particular, single-sided interferograms should be used to avoid large noise bursts, and phase ambiguities must be resolved in uncalibrated spectra before radiometric calibration. The corrections are essential for studies that require accurately calibrated radiance spectra, including those that track atmospheric changes globally on decadal time scales. [c] 2010 Optical Society of America OCIS codes: 300.6300, 120.3180, 280.4991, 290.6815, 120.6085.

Profiles of atmospheric temperature and water vapor from remotely sensed platforms provide critical observations within the temporal and spatial gaps of the radiosonde network. The 2017 National Academies of Science Decadal Survey highlighted that observations of the planetary boundary layer (PBL) from the current space-based observing system are not of the necessary accuracy or resolution for monitoring and predicting high-impact weather phenomena. One possible solution to improving observations of the PBL is supplementing the existing space-based observing system with a network of ground-based profilers. A synthetic information content study is developed utilizing profiles from the Atmospheric Radiation Measurement (ARM) program sites at the Southern Great Plains (SGP), east North Atlantic (ENA), and North Slope of Alaska (NSA) to assess the benefits, in terms of degrees of freedom (DOF), vertical resolution, and uncertainties, of a synergy between the ground-based Atmospheric Emitted Radiance Interferometer (AERI) with space-based hyperspectral infrared (IR) sounders. A combination of AERI with any of the three polar-orbiting IR sounders: the Atmospheric Infrared Sounder (AIRS), the Cross-track Infrared Sounder (CrIS), or the Infrared Atmospheric Sounding Interferometer (IASI), results in a DOF increase of 30%–40% in the surface-to-700-hPa layer compared to the space-based instrument alone. Introducing AERI measurements to the observing system also results in significant improvements to vertical resolution and uncertainties in the bottom 1000 m of the atmosphere compared to CrIS measurements alone. A synergy of CrIS and AERI exceeds the 1-km-vertical-resolution goal set by the Decadal Survey in the lowest 1000 m. [ABSTRACT FROM AUTHOR]

Trade-off studies on spectral coverage, signal-to-noise ratio (SNR), and spectral resolution for a hyperspectral infrared (IR) sounder on a geostationary satellite are summarized. The data density method is applied for the vertical resolution analysis, and the rms error between true and retrieved profiles is used to represent the retrieval accuracy. The effects of spectral coverage, SNR, and spectral resolution on vertical resolution and retrieval accuracy are investigated. The advantages of IR and microwave sounder synergy are also demonstrated. When focusing on instrument performance and data processing, the results from this study show that the preferred spectral coverage combines long-wave infrared (LWIR) with the shorter middle-wave IR (SMidW). Using the appropriate spectral coverage, a hyperspectral IR sounder with appropriate SNR can achieve the required science performance (1 km vertical resolution, 1 K temperature, and 10% relative humidity retrieval accuracy). The synergy of microwave and IR sounders can improve the vertical resolution and retrieval accuracy compared to either instrument alone. OCIS codes: 010.0010, 010.1280, 120.0280, 120.6200.

Mucosal eosinophils increase in a number of gastrointestinal diseases that are often associated with altered epithelial barrier function, including food allergic enteropathies and inflammatory bowel diseases. Although eosinophils are known to secrete biologically active mediators including granule proteins, their role in gastrointestinal diseases is uncertain. The aim of this study was to determine the impact of eosinophils on intestinal barrier function. Epithelial barrier function was determined in a coculture of eosinophils and T84 epithelial cells and in a routine model of T helper (Th) type 2-mediated colitis. Coculture conditions resulted in decreased transepithelial resistance (TER) and increased transepithelial flux. Cell-free coculture supematants contained a [greater than or equal to]5-kDa soluble factor that also diminished TER; these supernatants contained the eosinophil-granule proteins major basic protein (MBP) and eosinophil-derived neurotoxin (EDN). T84 barrier function decreased significantly when basolateral surfaces were exposed to native human MBP but not EDN. Additional studies identified downregulation of the tight junctional molecule occludin as at least one mechanism for MBP action. MBP-null mice were protected from inflammation associated with oxazolone colitis compared with wild-type mice. In conclusion, MBP decreases epithelial barrier function and in this manner contributes to the pathogenesis of inflammatory bowel diseases. tight junction; eosinophilic gastroenteritis; food allergy

The theoretical basis is explored for inferring the microphysical properties of ice clouds from high spectral resolution infrared (IR) observations. Extensive radiative transfer simulations are carried out to address relevant issues. The single-scattering properties of individual ice crystals are computed from state-of-the-art light scattering computational methods and are subsequently averaged for 30 in situ particle size distributions and for four additional analytical Gamma size distributions. The nonsphericity of ice crystals is shown to have a significant impact on the radiative signatures in the IR spectrum. Furthermore, the errors associated with the use of the Henyey-Greenstein phase function can be larger than 1 K in terms of brightness temperature for large particle effective sizes (~ 80 [micro]m) at wavenumbers where the scattering of the IR radiation by ice crystals is not negligible. The simulations undertaken in this paper show that the slope of the IR brightness temperature spectrum between 790-960 [cm.sup.-1] is sensitive to the effective particle size. Furthermore, a strong sensitivity of the IR brightness temperature to cloud optical thickness is noted within the 1050-1250-[cm.sup.-1] region. Based on these spectral features, a technique is presented for the simultaneous retrieval of the visible optical thickness and effective particle size from high spectral resolution IR data for ice clouds. An error analysis shows that the uncertainties of the retrieved optical thickness and effective particle size have a small range of variation. The error for retrieving particle size in conjunction with an uncertainty of 5 K in cloud temperature, or a surface temperature uncertainty of 2.5 K, is less than 15%. The corresponding errors in the uncertainty of optical thickness are within 5% to 20%, depending on the value of cloud optical thickness. The applicability of the present retrieval technique is demonstrated using airborne high-resolution IR measurements obtained during two field campaigns. Index Terms--Ice Clouds, infrared spectrum, retrieval.