Chemoenzymatic Synthesis of Keratan Sulfate Oligosaccharides Using UDP-Galactose-6-aldehyde To Control Sulfation at Galactosides.

Keratan sulfate (KS) is a highly complex proteoglycan that has a poly-LacNAc chain that can be modified by diverse patterns of sulfate esters at C-6 positions of galactoside (Gal) and -acetylglucosamine (GlcNAc) residues. Here, a chemo-enzymatic methodology is described that can control the pattern of sulfation at Gal using UDP-Gal-aldehyde as a donor for poly-LacNAc assembly to temporarily block specific sites from sulfation by galactose 6-sulfotransferase (CHST1).

Labeling of Mucin-Type -Glycans for Quantification Using Liquid Chromatography and Fluorescence Detection.

-glycosylation is a common post-translational modification that is essential for the defensive properties of mucus barriers. Incomplete and altered -glycosylation is often linked to severe diseases, such as cancer, cystic fibrosis, and chronic obstructive pulmonary disease. Originating from a nontemplate-driven biosynthesis, mucin-type -glycan structures are very complex.

Ensemble machine learning model trained on a new synthesized dataset generalizes well for stress prediction using wearable devices.

Introduction: Advances in wearable sensor technology have enabled the collection of biomarkers that may correlate with levels of elevated stress. While significant research has been done in this domain, specifically in using machine learning to detect elevated levels of stress, the challenge of producing a machine learning model capable of generalizing well for use on new, unseen data remain. Acute stress response has both subjective, psychological and objectively measurable, biological components that can be expressed differently from person to person, further complicating the development of a generic stress measurement model.

Exploiting Substrate Specificities of 6--Sulfotransferases to Enzymatically Synthesize Keratan Sulfate Oligosaccharides.

Keratan sulfate (KS) is a glycosaminoglycan that is widely expressed in the extracellular matrix of various tissue types, where it is involved in many biological processes. Herein, we describe a chemo-enzymatic approach to preparing well-defined KS oligosaccharides by exploiting the known and newly discovered substrate specificities of relevant sulfotransferases. The premise of the approach is that recombinant GlcNAc-6--sulfotransferases (CHST2) only sulfate terminal GlcNAc moieties to give GlcNAc6S that can be galactosylated by B4GalT4.

Chemo-Enzymatic Synthesis of Isomeric I-branched Polylactosamines Using Traceless Blocking Groups.

Poly-N-acetyl lactosamines (polyLacNAc) are common structural motifs of N- and O-linked glycan, glycosphingolipids and human milk oligosaccharides. They can be branched by the addition of β1,6-linked N-acetyl-glucosamine (GlcNAc) moieties to internal galactoside (Gal) residues by the I-branching enzyme beta-1,6-N-acetylglucosaminyltransferase 2 (GCNT2). I-branching has been implicated in many biological processes and is also associated with various diseases such as cancer progression.

Sialic acid O-acetylation patterns and glycosidic linkage type determination by ion mobility-mass spectrometry.

O-acetylation is a common modification of sialic acids that has been implicated in a multitude of biological and disease processes. A lack of analytical methods that can determine exact structures of sialic acid variants is a hurdle to determine roles of distinct O-acetylated sialosides. Here, we describe a drift tube ion mobility-mass spectrometry approach that can elucidate exact O-acetylation patterns as well as glycosidic linkage types of sialosides isolated from complex biological samples.

Ultrafast RNA extraction-free SARS-CoV-2 detection by direct RT-PCR using a rapid thermal cycling approach.

The COVID19 pandemic has underlined the need for quick and high-throughput SARS-CoV-2 detection assays. Here we report the development of a direct RT-PCR detection method that can reliably detect SARS-CoV-2 gRNA in nasopharyngeal swab samples in under 27 minutes without needing nucleic acid extraction. Fluorescence readouts were highly linear, robust, and sensitive with a LoD95% of determined at 1.

Oxidative Release of -Glycans under Neutral Conditions for Analysis of Glycoconjugates Having Base-Sensitive Substituents.

Protein -glycosylation is one of the most diverse post-translational modifications. A critical step in the analysis of -glycomes is the release of glycans from glycoconjugates. Current release methods rely mainly on β-elimination, which can result in peeling reactions and loss of base-sensitive functionalities leading to misidentification of glycans.

Receptor Density-Dependent Motility of Influenza Virus Particles on Surface Gradients.

Influenza viruses can move across the surface of host cells while interacting with their glycocalyx. This motility may assist in finding or forming locations for cell entry and thereby promote cellular uptake. Because the binding to and cleavage of cell surface receptors forms the driving force for the process, the surface-bound motility of influenza is expected to be dependent on the receptor density.

Generalizable machine learning for stress monitoring from wearable devices: A systematic literature review.

Introduction: Wearable sensors have shown promise as a non-intrusive method for collecting biomarkers that may correlate with levels of elevated stress. Stressors cause a variety of biological responses, and these physiological reactions can be measured using biomarkers including Heart Rate Variability (HRV), Electrodermal Activity (EDA) and Heart Rate (HR) that represent the stress response from the Hypothalamic-Pituitary-Adrenal (HPA) axis, the Autonomic Nervous System (ANS), and the immune system. While Cortisol response magnitude remains the gold standard indicator for stress assessment [1], recent advances in wearable technologies have resulted in the availability of a number of consumer devices capable of recording HRV, EDA and HR sensor biomarkers, amongst other signals.

Nasal and Nasopharyngeal Rosai-Dorfman Disease.

Nasal and nasopharyngeal Rosai-Dorfman disease is a rare cause of nasal obstruction.

Metabolic labeling of the bacterial peptidoglycan by functionalized glucosamine.

-Acetylglucosamine (GlcNAc) is an essential monosaccharide required in almost all organisms. Fluorescent labeling of the peptidoglycan (PG) on -acetylglucosamine has been poorly explored. Here, we report on the labeling of the PG with a bioorthogonal handle on the GlcNAc.

Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial.

Introduction: The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI).

Objective: In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel.

Methods: A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y inhibitor strategy in patients with myocardial infarction undergoing primary PCI.

Efficacy and safety of glycoprotein IIb/IIIa inhibitors in addition to P2Y inhibitors in ST-segment elevation myocardial infarction: A subanalysis of the POPular Genetics trial.

Background: Glycoprotein IIb/IIIa inhibitors (GPI) are still used in patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI), although discussion about its clinical benefit is ongoing.

Methods: GPI use was analyzed in this subanalysis of the POPular Genetics trial, which randomized STEMI patients to CYP2C19 genotype-guided treatment (clopidogrel or ticagrelor) or standard treatment with ticagrelor/prasugrel. The composite thrombotic endpoint consisted of cardiovascular death, myocardial infarction (MI), definite stent thrombosis, and stroke at 30 days.

Race-specific characteristics in pediatric eosinophilic esophagitis in an urban inner-city clinic.

Background: Manifestations of pediatric eosinophilic esophagitis (EoE) are varied and dictated by multiple factors. The influence of race is limited to small observational cohorts of dichotomized data (Whites vs non-Whites) or single-racial analysis.

Objective: To better understand phenotypic variability in the manifestation and atopic sensitization of pediatric EoE, from the perspective of race.

Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.

Background: Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.

Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis.

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Eosinophilia in Asthma Patients Is Protective Against Severe COVID-19 Illness.

Background: There is a paucity of information on coronavirus disease 2019 (COVID-19) outcomes in asthmatics.

Objective: To identify risk factors associated with admission and subsequent mortality among COVID-19-infected asthmatics.

Methods: Adults at our institution with a positive polymerase chain reaction for COVID-19 between March 14 and April 27, 2020, were retrospectively identified.

A randomized trial of subcutaneous allergy immunotherapy in inner-city children with asthma less than 4 years of age.

Background: Allergic sensitization to environmental allergens in the first years of life is a strong predictor of asthma morbidity in children. Allergy immunotherapy can improve asthma and allergy outcomes, but its efficacy in inner-city, atopic children of less than 4 years of age with recurrent wheezing has not yet been established.

Objective: To determine whether subcutaneous allergy immunotherapy improves asthma in a population of US inner-city children when started at less than 4 years of age.

Hierarchical Multivalent Effects Control Influenza Host Specificity.

Understanding how emerging influenza viruses recognize host cells is critical in evaluating their zoonotic potential, pathogenicity, and transmissibility between humans. The surface of the influenza virus is covered with hemagglutinin (HA) proteins that can form multiple interactions with sialic acid-terminated glycans on the host cell surface. This multivalent binding affects the selectivity of the virus in ways that cannot be predicted from the individual receptor-ligand interactions alone.