Dengue Virus Serotype 1 Conformational Dynamics Confers Virus Strain-Dependent Patterns of Neutralization by Polyclonal Sera.

Dengue virus cocirculates globally as four serotypes (DENV1 to -4) that vary up to 40% at the amino acid level. Viral strains within a serotype further cluster into multiple genotypes. Eliciting a protective tetravalent neutralizing antibody response is a major goal of vaccine design, and efforts to characterize epitopes targeted by polyclonal mixtures of antibodies are ongoing.

Pulmonary receptor for advanced glycation end-products promotes asthma pathogenesis through IL-33 and accumulation of group 2 innate lymphoid cells.

Background: Single nucleotide polymorphisms in the human gene for the receptor for advanced glycation end-products (RAGE) are associated with an increased incidence of asthma. RAGE is highly expressed in the lung and has been reported to play a vital role in the pathogenesis of murine models of asthma/allergic airway inflammation (AAI) by promoting expression of the type 2 cytokines IL-5 and IL-13. IL-5 and IL-13 are prominently secreted by group 2 innate lymphoid cells (ILC2s), which are stimulated by the proallergic cytokine IL-33.

Clearance kinetics and matrix binding partners of the receptor for advanced glycation end products.

Elucidating the sites and mechanisms of sRAGE action in the healthy state is vital to better understand the biological importance of the receptor for advanced glycation end products (RAGE). Previous studies in animal models of disease have demonstrated that exogenous sRAGE has an anti-inflammatory effect, which has been reasoned to arise from sequestration of pro-inflammatory ligands away from membrane-bound RAGE isoforms. We show here that sRAGE exhibits in vitro binding with high affinity and reversibly to extracellular matrix components collagen I, collagen IV, and laminin.

The receptor for advanced glycation end products is a central mediator of asthma pathogenesis.

The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been shown to contribute to the pathogenesis of diabetes, atherosclerosis, and neurodegeneration. However, its role in asthma and allergic airway disease is largely unknown. These studies use a house dust mite (HDM) mouse model of asthma/allergic airway disease.

Lack of the receptor for advanced glycation end-products attenuates E. coli pneumonia in mice.

Background: The receptor for advanced glycation end-products (RAGE) has been suggested to modulate lung injury in models of acute pulmonary inflammation. To study this further, model systems utilizing wild type and RAGE knockout (KO) mice were used to determine the role of RAGE signaling in lipopolysaccharide (LPS) and E. coli induced acute pulmonary inflammation.

Paradoxical function for the receptor for advanced glycation end products in mouse models of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor survival. The identification of therapeutic targets is essential to improving outcomes. Previous studies found that expression of the receptor for advanced glycation end products (RAGE) in the lung is significantly decreased in human IPF lungs and in two animal models of pulmonary fibrosis.

Tolerance to isoflurane does not occur in developing Xenopus laevis tadpoles.

Introduction: Tolerance is observed for a variety of central nervous system depressants including ethanol, which is an anesthetic, but has not been convincingly demonstrated for a potent halogenated volatile anesthetic. Failure to demonstrate tolerance to these agents may be the result of inadequate exposure to anesthetic. In this study, we exposed Xenopus laevis tadpoles to surgical anesthetic concentrations of isoflurane for 1 wk.

Anesthetic properties of the ketone bodies beta-hydroxybutyric acid and acetone.

Background: We tested the hypothesis that two metabolites that are elevated in ketosis (beta-hydroxybutyric acid, and acetone) modulate ion channels in a manner similar to anesthetics and produce anesthesia in animals.

Methods: alpha1beta2gamma2sgamma-aminobutyric acid type A (GABA(A)), alpha1 glycine, NR1/NR2A N-methyl-d-aspartate, and two pore domain TRESK channels were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. The effect of beta hydroxybutyric acid and acetone on channel function was measured.

The plasticizer di(2-ethylhexyl) phthalate modulates gamma-aminobutyric acid type A and glycine receptor function.

Introduction: Intravenous (IV) fluid bags made of polyvinyl chloride (PVC) often contain the plasticizer di(2-ethylhexyl) phthalate (DEHP) to make the PVC flexible. Phthalate esters have been reported to inhibit neuronal nicotinic acetylcholine receptors, which are sensitive to many inhaled anesthetics. This raises the possibility that DEHP might modulate the function of other cys-loop receptors, such as gamma-amino butyric acid type A (GABA(A)) and glycine receptors, and that DEHP-plasticized PVC might interfere with electrophysiologic studies of anesthetic mechanisms on those receptors.

Anesthetic-like modulation of a gamma-aminobutyric acid type A, strychnine-sensitive glycine, and N-methyl-d-aspartate receptors by coreleased neurotransmitters.

Introduction: A mechanism of anesthesia has recently been proposed which predicts that coreleased neurotransmitters may modulate neurotransmitter receptors for which they are not the native agonist in a manner similar to anesthetics.

Methods: We tested this prediction by applying acetylcholine to a NR1/NR2A N-methyl-d-aspartate receptor, glycine to a wild-type alpha(1)beta(2) and anesthetic-resistant alpha(1)(S270I)beta(2) gamma-amino-butyric acid (GABA) type A receptor, and GABA to a homomeric alpha(1) wild type and anesthetic-resistant alpha(1) S267I glycine receptor. Receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping.

Ammonia has anesthetic properties.

Background: A recent theory of anesthesia predicts that some endogenous compounds should have anesthetic properties. This theory raises the possibility that metabolites that are profoundly elevated in disease may also exert anesthetic effects. Because in pathophysiologic concentrations, ammonia reversibly impairs memory, consciousness, and responsiveness to noxious stimuli in a manner similar to anesthetics, we investigated whether ammonia had anesthetic properties.