Meteosat Third Generation (MTG) Holmlund, K.; Grandell, J.; Schmetz, J. ...
Bulletin of the American Meteorological Society,
05/2021, Letnik:
102, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Within the next couple of years, the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) will start the deployment of its next-generation geostationary meteorological ...satellites. The Meteosat Third Generation (MTG) is composed of four imaging (MTG-I) and two sounding (MTG-S) platforms. The satellites are three-axis stabilized, unlike the two previous generations of Meteosat that were spin stabilized, and carry two sets of remote sensing instruments each. Hence, in addition to providing continuity, the new system will provide an unprecedented capability from geostationary orbit. The payload on the MTG-I satellites are the 16-channel Flexible Combined Imager (FCI) and the Lightning Imager (LI). The payloads on the MTG-S satellites are the hyperspectral Infrared Sounder (IRS) and a high-resolution Ultraviolet–Visible–Near-Infrared (UVN) sounder Sentinel-4/UVN, provided by the European Commission. Today, hyperspectral sounding from geostationary orbit is provided by the Chinese Fengyun-4A (FY-4A) satellite Geostationary Interferometric Infrared Sounder (GIIRS) instrument, and lightning mappers are available on FY-4A and on the National Oceanic and Atmospheric Administration (NOAA) GOES-16 and GOES-17 satellites. Consequently, the development of science and applications for these types of instruments have a solid foundation. However, the IRS, LI, and Sentinel-4/UVN are a challenging first for Europe in a geostationary orbit. The four MTG-I and two MTG-S satellites are designed to provide 20 and 15.5 years of operational service, respectively. The launch of the first MTG-I is expected at the end of 2022 and the first MTG-S roughly a year later. This article describes the four instruments, outlines products and services, and addresses the evolution of the further applications.
Most human Siglecs (sialic acid binding immunoglobulin-like lectins) are expressed on the surfaces of overlapping subsets of immune cells, and most carry immunoreceptor tyrosine-based inhibitory ...domains on their intracellular motifs. When immune inhibitory Siglecs bind to complementary sialoglycans in their local milieu, engagement results in down-regulation of the immune response. Siglecs have come under scrutiny as potential targets of drugs to modify the course of inflammation (and other immune system responses) and as immune checkpoints in cancer. Human Siglecs bind to endogenous human sialoglycans. The identities of these endogenous human sialoglycan immune regulators are beginning to emerge, along with some general principles that may inform future investigations in this area. Among these principles is the finding that a cell type or tissue may express a ligand for a particular Siglec on a single or a very few of its sialoglycoproteins. The selected protein carrier for a particular Siglec may be unique in a certain tissue, but vary tissue-to-tissue. The binding affinity of endogenous Siglec ligands may surpass that of its binding to synthetic sialoglycan determinants by several orders of magnitude. Since most human Siglecs have evolved rapidly and are distinct from those in most other mammals, this review describes endogenous human Siglec ligands for several human immune inhibitory Siglecs. As the identities of these immune regulatory sialoglycan ligands are defined, additional opportunities to target Siglecs therapeutically may emerge.
•Immune inhibitory Siglecs on the surface of human immune cells engage Siglec ligands in their local tissue environment.•Siglec ligands may be cell surface or secreted sialoglycans (glycoproteins or glycolipids).•Siglec ligands are often distinctive sialoglycans carried on a restricted number of glycoproteins in each target tissue.•Siglec ligands may be minor glycoforms of common glycoproteins in which the carrier protein plays an ancillary function.•Siglec ligand research focuses on their roles in immune regulation and as immune checkpoint inhibitors in cancer.
The immunoinhibitory receptor Siglec-8 on the surface of human eosinophils and mast cells binds to sialic acid–containing ligands in the local milieu, resulting in eosinophil apoptosis, inhibition of ...mast cell degranulation, and suppression of inflammation. Siglec-8 ligands were found on postmortem human trachea and bronchi and on upper airways in 2 compartments, cartilage and submucosal glands, but they were surprisingly absent from the epithelium. We hypothesized that Siglec-8 ligands in submucosal glands and ducts are normally transported to the airway mucus layer, which is lost during tissue preparation.
Our aim was to identify the major Siglec-8 sialoglycan ligand on the mucus layer of human airways.
Human upper airway mucus layer proteins were recovered during presurgical nasal lavage of patients at a sinus clinic. Proteins were resolved by gel electrophoresis and blotted, and Siglec-8 ligands detected. Ligands were purified by size exclusion and affinity chromatography, identified by proteomic mass spectrometry, and validated by electrophoretic and histochemical colocalization. The affinity of Siglec-8 binding to purified human airway ligand was determined by inhibition of glycan binding.
A Siglec-8-ligand with a molecular weight of approximately 1000 kDa was found in all patient nasal lavage samples. Purification and identification revealed deleted in malignant brain tumors 1 (DMBT1) (also known by the aliases GP340 and SALSA), a large glycoprotein with multiple O-glycosylation repeats. Immunoblotting, immunohistochemistry, and enzyme treatments confirmed that Siglec-8 ligand on the human airway mucus layer is an isoform of DMBT1 carrying O-linked sialylated keratan sulfate chains (DMBT1S8). Quantitative inhibition revealed that DMBT1S8 has picomolar affinity for Siglec-8.
A distinct DMBT1 isoform, DMBT1S8, is the major high-avidity ligand for Siglec-8 on human airways.
Display omitted
Hepatitis B virus birth dose (HepB-BD) vaccination is recommended to reduce mother to infant transmission. We evaluated the HepB-BD status of women who gave birth between 2011 and 2016 (N = 3,583) ...using the 2015-2016 Myanmar Demographic and Health Survey.
Frequency distributions of HepB-BD vaccination across maternal and health system factors, concentration indices, and logistic regression models were used to estimate coverage, inequity, and factors associated with vaccination.
The majority of participants were younger than 30 years of age, lived in rural areas, and were multiparous. Almost all received antenatal care (ANC), but only 43% received recommended ANC services, and 60% gave birth at home. The overall HepB-BD coverage rate was 26%. Vaccination coverage was higher in urban areas and was inequitably concentrated among children of more educated and wealthier women. HepB-BD coverage was also positively associated with receipt of ANC at non-governmental facilities, and delivery at a facility, skilled provider at birth and Cesarean delivery. After adjusting for sociodemographic and health system factors, receipt of the HepB-BD was positively associated with weekly media exposure, receipt of recommended ANC, and Cesarean delivery, and inversely associated with home delivery.
Both socioeconomic and health systems factors influenced suboptimal and inequitable vaccination coverage. Improved access to quality ANC and delivery services may increase HepB-BD coverage although targeted approaches to reach home births are likely required to achieve national goals.
Abstract
Siglec-8, an immune-inhibitory sialoglycan binding lectin (S8), is expressed on the surface of eosinophils and mast cells, which are potent mediators of allergic inflammation. When S8 ...engages endogenous sialoglycan ligands, eosinophils undergo apoptosis and mast cell mediator release is inhibited. In the human airway, Siglec-8 ligands (S8L) are sialylated keratan sulfate chains carried on isoforms of the protein Deleted in Malignant Brain Tumors-1 (DMBT1), an immunoregulatory protein that we recently identified as the endogenous ligand for S8, DMBT1S8. We herein report that S8L is overexpressed in chronic rhinosinusitis with nasal polyposis (CRSwNP), a prevalent eosinophilic laden airway disease. Quantification and comparison of the degree to which DMBT1 carries the S8L by immunoblot analysis and lectin blot overlay, respectively, from nasal lavage showed that the S8L/DMBT1 ratio was significantly increased in CRSwNP vs. control or CRS patients. We identified the histological sites of S8L and DMBT1 expression in fresh surgically resected human nasal polyps. Histochemistry of diseased polyps and adjacent nondiseased middle turbinate (MT) tissue from CRSwNP demonstrated colocalization of S8L and DMBT1 with highest staining in submucosal glands >> epithelium > stoma. S8L expression was specifically elevated in the submucosal glands and epithelium of polyp tissue compared to MT. We hypothesize that expression of the isoform of DMBT1 carrying the Siglec-8 binding sialoglycan, DMBT1S8, is induced in polyps of CRSwNP specifically at the site of disease, is produced in the submucosal glands of polyps and secreted into the lumen of the sinonasal cavity as a host response to mitigate eosinophil-mediated inflammation.
Abstract
Background
There are many well-described potential gastrointestinal (GI) side effects of pancreatic resection that can cause patients to suffer from chronic malabsorption, diarrhea, and ...persistent nausea. These GI symptoms can affect postoperative recovery, initiation of adjuvant therapy, and overall quality of life (QOL). The purpose of this study is to quantify the incidence of post-procedural complications and identify patients at higher risk for experiencing GI dysfunction after pancreatectomy.
Methods
A retrospective review of patients who underwent pancreatic resection at a single institution between January 2014 and December 2019 was performed. Demographics, operative factors, and postoperative gastrointestinal symptomatology and treatments were obtained by chart review. Significance tests were performed to compare GI dysfunction between patient subgroups.
Results
A total of 545 patients underwent pancreatic resection; within the cohort 451 patients (83%) underwent a pancreaticoduodenectomy (PD) and the most common indication was pancreatic adenocarcinoma. Two-thirds of patients (67%) reported gastrointestinal symptoms persisting beyond hospitalization. Only 105 patients (20%) were referred to gastroenterology for evaluation with 30 patients (5.5%) receiving a formal diagnosis. Patients who underwent PD were more likely to report GI symptoms and patients who identified as Caucasian were more likely to be referred to gastroenterology for evaluation.
Conclusions
Gastrointestinal dysfunction after pancreatic resection occurs frequently yet only a small percentage of patients are referred for formal testing and diagnosis. There also appears to be a racial difference in referral patterns. Patients would benefit if earlier attention was dedicated to the diagnosis and corresponding treatment for postoperative digestive health disorders to optimize treatment planning and QOL.
Alzheimer’s disease (AD) is characterized by accumulation of misfolded proteins. Genetic studies implicate microglia, brain-resident phagocytic immune cells, in AD pathogenesis. As positive ...effectors, microglia clear toxic proteins, whereas as negative effectors, they release proinflammatory mediators. An imbalance of these functions contributes to AD progression. Polymorphisms of human CD33, an inhibitory microglial receptor, are linked to AD susceptibility; higher CD33 expression correlates with increased AD risk. CD33, also called Siglec-3, is a member of the sialic acid–binding immunoglobulin-type lectin (Siglec) family of immune regulatory receptors. Siglec-mediated inhibition is initiated by binding to complementary sialoglycan ligands in the tissue environment. Here, we identify a single sialoglycoprotein in human cerebral cortex that binds CD33 as well as Siglec-8, the most abundant Siglec on human microglia. The ligand, which we term receptor protein tyrosine phosphatase zeta (RPTPζ)S3L, is composed of sialylated keratan sulfate chains carried on a minor isoform/glycoform of RPTPζ (phosphacan) and is found in the extracellular milieu of the human brain parenchyma. Brains from human AD donors had twofold higher levels of RPTPζS3L than age-matched control donors, raising the possibility that RPTPζS3L overexpression limits misfolded protein clearance contributing to AD pathology. Mice express the same structure, a sialylated keratan sulfate RPTPζ isoform, that binds mouse Siglec-F and crossreacts with human CD33 and Siglec-8. Brains from mice engineered to lack RPTPζ, the sialyltransferase St3gal4, or the keratan sulfate sulfotransferase Chst1 lacked Siglec binding, establishing the ligand structure. The unique CD33 and Siglec-8 ligand, RPTPζS3L, may contribute to AD progression.
With the increasing demand for blood transfusions, the production of human hemoglobin (Hb) from sustainable sources is increasingly studied. Microbial production is an attractive option, as it may ...provide a cheap, safe, and reliable source of this protein. To increase the production of human hemoglobin by the yeast Saccharomyces cerevisiae, the degradation of Hb was reduced through several approaches. The deletion of the genes HMX1 (encoding heme oxygenase), VPS10 (encoding receptor for vacuolar proteases), PEP4 (encoding vacuolar proteinase A), ROX1 (encoding heme-dependent repressor of hypoxic genes) and the overexpression of the HEM3 (encoding porphobilinogen deaminase) and the AHSP (encoding human alpha-hemoglobin-stabilizing protein) genes — these changes reduced heme and Hb degradation and improved heme and Hb production. The reduced hemoglobin degradation was validated by a bilirubin biosensor. During glucose fermentation, the engineered strains produced 18% of intracellular Hb relative to the total yeast protein, which is the highest production of human hemoglobin reported in yeast. This increased hemoglobin production was accompanied with an increased oxygen consumption rate and an increased glycerol yield, which (we speculate) is the yeast's response to rebalance its NADH levels under conditions of oxygen limitation and increased protein-production.
•The sequential hemoglobin production optimization increased yeast cell volume.•Reducing the degradation of heme and hemoglobin decreased bilirubin formation.•Reducing the degradation yielded 18% of intracellular protein as human hemoglobin.•Engineered strain is suitable for the secretion of the hemoglobin to the medium.
Debaryomyces hansenii is traditionally described as a halotolerant non‐conventional yeast and has served as a model organism for the study of osmotolerance and salt tolerance mechanisms in eukaryotic ...systems for the past 30 years. However, unraveling of D. hansenii's biotechnological potential has always been difficult due to the persistent limitations in the availability of efficient molecular tools described for this yeast. Additionally, there is a lack of consensus and contradictory information along the recent years that limits a comprehensive understanding of its central carbon metabolism, mainly due to a lack of physiological studies in controlled and monitored environments. Moreover, there is little consistency in the culture conditions (media composition, temperature, and pH among others) used by different groups, which makes it complicated when trying to get prevalent conclusions on behavioral patterns. In this work, we present for the first time a characterization of D. hansenii in batch cultivations using highly controlled lab‐scale bioreactors. Our findings contribute to a more complete picture of the central carbon metabolism and the external pH influence on the yeast's ability to tolerate high Na+ and K+ concentrations, pointing to a differential effect of both salts, as well as a positive effect in cell performance when low environmental pH values are combined with a high sodium concentration in the media. Finally, a novel survival strategy at very high salinity (2 M) is proposed for this yeast, as well as potential outcomes for its use in industrial biotechnology applications.
Take Away
High salt concentrations stimulate respiration in Debaryomyces hansenii.
Sodium exerts a stronger positive impact on cell performance than potassium.
μmax is higher at a combination of low pH, high salt, and high temperature.
Concentrations of 2 M salt result in slower growth but increased biomass yield.
The positive effect of salts is enhanced at low glucose concentration.
A controlled batch cultivation of the “salt‐loving” yeast Debaryomyces hansenii in a highly instrumented lab‐scale bioreactor, at the DTU Fermentation core lab (Technical University of Denmark).
Nifedipine and FPL 64176 (FPL), which block and potentiate L-type voltage-gated Ca
channels, respectively, modulate Ca
1.2 more potently than Ca
1.3. To identify potential strategies for developing ...subtype-selective inhibitors, we investigated the role of divergent amino acid residues in transmembrane domains IIIS5 and the extracellular IIIS5-3P loop region in modulation of these channels by nifedipine and FPL. Insertion of the extracellular IIIS5-3P loop from Ca
1.2 into Ca
1.3 (Ca
1.3+) reduced the IC
of nifedipine from 289 to 101 nM, and substitution of S1100 with an A residue, as in Ca
1.2, accounted for this difference. Substituting M1030 in IIIS5 to V in Ca
1.3+ (Ca
1.3+V) further reduced the IC
of nifedipine to 42 nM. FPL increased current amplitude with an EC
of 854 nM in Ca
1.3, 103 nM in Ca
1.2, and 99 nM in Ca
1.3+V. In contrast to nifedipine block, substitution of M1030 to V in Ca
1.3 had no effect on potency of FPL potentiation of current amplitude, but slowed deactivation in the presence and absence of 10
M FPL. FPL had no effect on deactivation of Ca
1.3/dihydropyridine-insensitive (DHPi), a channel with very low sensitivity to nifedipine block (IC
∼93
M), but did shift the voltage-dependence of activation by ∼-10 mV. We conclude that the M/V variation in IIIS5 and the S/A variation in the IIIS5-3P loop of Ca
1.2 and Ca
1.3 largely determine the difference in nifedipine potency between these two channels, but the difference in FPL potency is determined by divergent amino acids in the IIIS5-3P loop.
PDF
