New approaches to immunotherapy in house dust mite allergy

Allergen immunotherapy (AIT) has developed over the last few decades and has emerged as a promising treatment. House dust mite (HDM) is a target allergen in AIT, and various modified HDM allergens have been improved for their efficacy. Moreover, clinical trials have proved their significantly therapeutic effects in allergy. This article review focuses on HDM allergens developed for AIT efficacy, and determines that their action mechanisms are strongly based on immune tolerance. Treatments for HDM allergens have been optimized by modification or/and addition of adjuvants, and clinically evaluated by subcutaneous and sublingual administration. Representative allergens used in AIT are chemically modified allergoids and recombinant allergens, including altered epitopes. The effective mechanisms subsequent to AIT include the suppressive actions of interleukin-10 and transforming growth factor-β secreted by regulatory cells, including regulatory T cells and regulatory B cells, and isotype switching from immunoglobulin E to immunoglobulin G4. Further studies of AIT are needed to achieve the milestone in treating allergies

Structure of AGCM-Simulated Convectively Coupled Kelvin Waves and Sensitivity to Convective Parameterization

A study of the convectively coupled Kelvin wave (CCKW) properties from a series of atmospheric general circulation model experiments over observed sea surface temperatures is presented. The simulations are performed with two different convection schemes (a mass flux scheme and a moisture convergence scheme) using a range of convective triggers, which inhibit convection in different ways. Increasing the strength of the convective trigger leads to significantly slower and more intense CCKW activity in both convection schemes. With the most stringent trigger in the mass flux scheme, the waves have realistic speed and variance and also exhibit clear shallow-to-deep-to-stratiform phase tilts in the vertical, as in observations. While adding a moisture trigger results in vertical phase tilts in the mass flux scheme, the moisture convergence scheme CCKWs show no such phase tilts even with a stringent convective trigger. The changes in phase speed in the simulations are interpreted using the concept of "gross moist stability" (GMS). Inhibition of convection results in a more unstable tropical atmosphere in the time mean, and convection is shallower on average as well. Both of these effects lead to a smaller GMS, which leads to slower propagation of the waves, as expected from theoretical studies. Effects such as changes in radiative heating, atmospheric humidity, and vertical velocity following the wave have a relatively small effect on the GMS as compared with the time mean state determined by the convection scheme.open222

Molecular Weight Dependent Glucose Lowering Effect of Low Molecular Weight Chitosan Oligosaccharide (GO2KA1) on Postprandial Blood Glucose Level in SD Rats Model

Abstract This research investigated the effect of enzymatically digested low molecular weight (MW) chitosan oligosaccharide on type 2 diabetes prevention. Three different chitosan oligosaccharide samples with varying MW were evaluated in vitro for inhibition of rat small intestinal α-glucosidase and porcine pancreatic α-amylase (GO2KA1; \u3c1000 Da, GO2KA2; 1000–10,000 Da, GO2KA3; MW \u3e 10,000 Da). The in vitro results showed that all tested samples had similar rat α-glucosidase inhibitory and porcine α-amylase inhibitory activity. Based on these observations, we decided to further investigate the effect of all three samples at a dose of 0.1 g/kg, on reducing postprandial blood glucose levels in Sprague-Dawley (SD) rat model after sucrose loading test. In the animal trial, all tested samples had postprandial blood glucose reduction effect, when compared to control, however GO2KA1 supplementation had the strongest effect. The glucose peak (Cmax) for GO2KA1 and control was 152 mg/dL and 193 mg/dL, respectively. The area under the blood glucose-time curve (AUC) for GO2KA1 and control was 262 h mg/dL and 305 h mg/dL, respectively. Furthermore, the time of peak plasma concentration of blood glucose (Tmax) for GO2KA1 was significantly delayed (0.9 h) compared to control (0.5 h). These results suggest that GO2KA1 could have a beneficial effect for blood glucose management relevant to diabetes prevention in normal and pre-diabetic individuals. The suggested mechanism of action is via inhibition of the carbohydrate hydrolysis enzyme α-glucosidase and since GO2KA1 (MW \u3c 1000 Da) had higher in vivo effect, we hypothesize that it is more readily absorbed and might exert further biological effect once it is absorbed in the blood stream, relevant to blood glucose management

Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells

AbstractLeukotactin-1 (Lkn-1)/CCL15 is a recently cloned CC-chemokine that binds to the CCR1 and CCR3. Although Lkn-1 has been known to function as a chemoattractant for neutrophils, monocytes and lymphocytes, its cellular mechanism remains unclear. To understand the mechanism of Lkn-1-induced chemotaxis signaling, we examined the chemotactic activities of human osteogenic sarcoma cells expressing CCR1 in response to Lkn-1 using inhibitors of signaling molecules. Inhibitors of Gi/Go protein, phospholipase C (PLC) and protein kinase Cδ (PKCδ) inhibited the chemotactic activity of Lkn-1 indicating that Lkn-1-induced chemotaxis signal is transduced through Gi/Go protein, PLC and PKCδ. The activities of PLC and PKCδ were also enhanced by Lkn-1 stimulation. Chemotactic activity of Lkn-1 was inhibited by the treatment of cycloheximide and actinomycin D suggesting that newly synthesized proteins are needed for chemotaxis. Nuclear factor-κB (NF-κB) inhibitor reduced chemotactic activity of Lkn-1. DNA binding activity of NF-κB was also enhanced by Lkn-1 stimulation. These results suggest that Lkn-1 transduces the signal through Gi/Go protein, PLC, PKCδ, NF-κB and newly synthesized proteins for chemotaxis

CHANGE IN SPATIOTEMPORAL CYCLE VARIABLES & MUSCLE ACTIVATION DURING CtASSlC ROLLER SKI DOUBLE POLING TECHNIQUE

The purpose of the study was to assess the effects of distance covered while roller skiing using the double poling technique. Five national team members and college elite cross-country skiers were chosen to participate in this study. EMG system and digital camcorder were used to measure spatiotemporal cycle variables, muscular fatigue, and activation patterns. There were no significant differences on cycle variables. However, the result shows accumulation of fatigue and decrease of muscle activation on triceps brachii and tibialis anterior muscles across skiing distance

Pedigree reconstruction and spatial analysis for genetic testing and selection in a Larix kaempferi (Lamb.) Carrière plantation

Larix kaempferi is one of the major timber species in Northeast Asia. Demand for the reforestation of the species is rising in South Korea due to an increase in large timber production and utilization. However, progeny trials for the species have not been explored, making it challenging to foster advanced generations of tree improvement. In the present study, genetic testing and selection for diameter growth were conducted using pedigree reconstruction and phenotypic spatial distribution analysis in a plantation of L. kaempferi. The aim of the present study was to select the superior larch individuals using the pedigree reconstruction and phenotypic spatial distribution to substitute progeny trials. The plantation of seed orchard crops was established in 1990 and one-hundred and eighty-eight trees were selected as the study material. Genetic variation was investigated first to validate its adequacy as breeding material. Genetic testing was carried out using a model considering pedigree information and spatial autoregression of the phenotypes. The expected heterozygosity of the mother trees and offspring were 0.672 and 0.681 presenting the corresponding level of genetic variation between two groups. The pedigree reconstruction using maternity analysis assigned one to six progenies to ninety-two candidate mothers. The accuracy of genetic testing was exceedingly increased with the animal model considering AR1 ⊗ AR1 structure compared to the animal model only. The estimated genetic variance of the former was 9.086 whereas that of the latter was 4.9E-5 for DBH. The predicted breeding values of the offspring for DBH were ranged from -5.937cm to 5.655cm and the estimated heritability of diameter growth was 0.344. The genetic testing approach based on pedigree reconstruction and phenotypic spatial distribution analysis was considered a useful analytical scheme that could replace or supplement progeny trials.K L and I-S K have a grant from the National Institute of Forest Science (NIFoS), Korea and K-S has a fnancial support (2020182B10-2022-BB01) from the Korea Forest Service

EFFECTS OF THREE PREPARATORY MOVEMENTS ON SIDEWARD PROPULSIVE MOVEMENT

This study investigated the effects of three preparatory movements (squat, countermovement and hopping) on the sideward propulsive movement. Seven subjects were analyzed in 3-D to determine how fast they reacted to external signals, using three techniques, to reacl1 an aIming spot. The hopping and the countermovement types were considered better than the squat type in the propulsion. The hopping particularly showed the shortest duration from the external signal to take-off and also recorded high extension moments due to the pre-stretch mechanism for the push-off phase

An autoregulatory loop controlling orphan nuclear receptor DAX-1 gene expression by orphan nuclear receptor ERRγ

The estrogen receptor-related receptor gamma (ERRγ/ERR3/NR3B3) is a member of the nuclear receptor superfamily that activates transcription in the absence of ligand. However, the detailed mechanism of gene regulation by ERRγ is not fully understood. In this study we have found that the orphan nuclear receptor ERRγ activates the DAX-1 promoter, which, in turn, represses transactivation by ERRγ. Serial deletions of mouse DAX-1 (mDAX-1) gene promoter have revealed that the region responding to ERRγ is located between −129 and −121 bp and −334 and −326 bp. Gel shift assays and chromatin immunoprecipitation (ChIP) assays demonstrated that ERRγ binds directly to the mDAX-1 promoter. Site-directed mutagenesis results demonstrated that ERRE1 (−129 to −121 bp) is more important than ERRE2 (−334 to −326 bp) which is not conserved in the human DAX-1 promoter. In addition, adenovirus-mediated overexpression of ERRγ induced DAX-1 gene expression in MCF-7 breast cancer cells that co-expressed ERRγ and DAX-1. Moreover, yeast two-hybrid and glutathione S-transferase (GST)-pull down assays demonstrated that DAX-1 physically interacted with ERRγ and inhibited ERRγ transactivation, and that this interaction was dependent on the AF-2 domain of ERRγ. In addition, in vitro competition assays showed that DAX-1 inhibited PGC-1α mediated ERRγ transactivation, via competition between these two factors for the AF-2 binding domain. We thus propose a novel autoregulatory loop that controls DAX-1 gene expression by ERRγ