Summary
Background
Genetic markers of susceptibility to asthma exacerbations in adults remain unclear.
Objective
To identify genetic markers of asthma exacerbations, particularly in patients with ...type‐2 inflammatory endotype.
Methods
In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin‐4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type‐2 inflammatory endotype) were considered in the analysis.
Results
Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type‐2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37–18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47–11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05–7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type‐2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type‐2 and neutrophilic inflammations.
Conclusions and Clinical Relevance
IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type‐2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.
Parental care in salamanders is thought to be simple and typically limited to female egg attendance. No elaborate preoviposition parental care had been described from salamanders. Recent studies ...revealed complex care behaviours by male Japanese giant salamanders (Andrias japonicus), a fully aquatic, secretive species with external fertilization. These studies emphasize behavioural convergence in paternal care between some of the fish species and the giant salamanders. The fish examples further imply the possibility that males of A. japonicus provide preoviposition parental care in the form of nest cleaning and building. We tested this possibility and also predicted that cleaning effort by a male salamander, if exists, would increase as it approaches the spawning event. Prior to the breeding season, large males (i.e. den masters) of A. japonicus occupy and guard suitable burrows well‐hidden along the stream bank. In the falls of 2012, 2013 and 2015, we videotaped and examined a single den master's pre‐ and postoviposition behaviours at Asa Zoological Park in Hiroshima, Japan. The den master repeatedly exhibited vigorous movements of front and hind limbs in a paddling motion at the bottom of the nest every day for the three separate years. The cleaning effort by the den master lineally increased as the spawning event approached, after which the den master completely ceased cleaning. With the cleaning behaviour, the den master made the den filled with debris including leaves and twigs buried in the sand. The floating debris was subsequently removed by the water current flowing through the nest. Water mould infection is a major cause of offspring mortality of aquatic amphibians including A. japonicus. By reducing the amount of organic matter that provides food sources for water mould, the nest cleaning likely reduces the risk of water mould infection among the offspring, serving as an important preoviposition parental care.
Our study provides the first quantitative description and analyses of elaborate preoviposition parental care in salamanders, in the form of nest cleaning by a male Japanese giant salamander (Andrias japonicus). A large male, called a den master, repeatedly exhibited vigorous movements of front and hind limbs in a paddling motion at the bottom of the nest every day prior to the spawning event. By reducing the amount of organic matter that provides food sources for water mould, the nest cleaning likely reduces the risk of water mould infection among the offspring.
Industrial mass production of nuclear emulsion film has been realized by the introduction of new photographic technologies.
In addition, emulsion-refreshing capability (erasing unwanted tracks before ...its use) was implemented by controlling the fading characteristics of the gel. The gel properties were optimized in order to satisfy this requirement; rapid track erasing at the erasing condition and minimum fading during the running of experiments.
Emulsion films with this capability are crucial for large-scale applications like the long base-line neutrino experiment, OPERA, which intend to detect Tau neutrino appearance at 732
km from the beam source.
Fine grained nuclear emulsion with several 10nm silver halide crystals can detect submicron tracks. This detector is expected to be worked as dark matter detector with directional sensitive. Now, ...nuclear emulsion became possible to be produced at Nagoya University, and extreme fine grained nuclear emulsion with 20nm diameter was produced. Using this emulsion and new reading out technique with expansion technique, for optical selection and X-ray microscopy, recoiled tracks induced by dark matter can be detected automatically. Then, readout efficiency is larger than 80% at 120nm, and angular resolution for final confirmation with X-ray microscopy is 20°. In addition, we started to construct the R&D underground facility in Gran Sasso.
This paper applies the heat balance equation (HBE) for clothed subjects as a linear function of mean skin temperature (t ₛₖ ) by a new sweating efficiency (η ₛw ) and an approximation for the ...thermoregulatory sweat rate. The equation predicting t ₛₖ in steady state conditions was derived as the solution of the HBE and used for a predictive heat strain scale. The heat loss from the wet clothing (WCL) area was identified with a new variable of ‘virtual dripping sweat rate VDSR’ (S wdᵣ ). This is a subject’s un-evaporated sweat rate in dry clothing from the regional sweat rate exceeding the maximum evaporative capacity, and adds the moisture to the clothing, reducing the intrinsic clothing insulation. The S wdᵣ allowed a mass balance analysis of the wet clothing area identified as clothing wetness (w cₗ ). The w cₗ was derived by combining the HBE at the WCL surface from which the evaporation rate and skin heat loss from WCL region are given. Experimental results on eight young male subjects wearing typical summer clothing, T-shirt and trousers verified the model for predicting t ₛₖ with WCL thermal resistance (R cₗ,w ) identified as 25 % of dry clothing (R cₗ,d ).
The present paper made the heat balance equation (HBE) for nude or minimally clad subjects a linear function of mean skin temperature (t ₛₖ) by applying new equations for sweating efficiency (η ₛw) ...and thermoregulatory sweat rate (S wR). As the solution of the HBE, the equation predicting t ₛₖ was derived and used for a heat strain scale of subjects. The η ₛw was proportional to the reciprocal of S w/E ₘₐₓ (S w, sweat rate; E ₘₐₓ maximum evaporative capacity) and the S wR was proportional to t ₛₖ with a parameter of the sweating capacity of the subject. The errors of predicted t ₛₖ from observations due to the approximation of η ₛw were examined based on experimental data conducted on eight young male subjects. The value of errors of t ₛₖ was −0.10 ± 0.42 °C (mean ± sample standard deviation (SSD)). We aim to apply the predicted t ₛₖ of a subject at a level of sweating capacity as a heat strain scale of a function of four environmental factors (dry- and wet-bulb temperatures, radiation, and air velocity) and three human factors (metabolic rate, sweating capacity, and clothing (≤0.2clo)).
We develop a formalism called a distributed constraint satisfaction problem (distributed CSP) and algorithms for solving distributed CSPs. A distributed CSP is a constraint satisfaction problem in ...which variables and constraints are distributed among multiple agents. Various application problems in distributed artificial intelligence can be formalized as distributed CSPs. We present our newly developed technique called asynchronous backtracking that allows agents to act asynchronously and concurrently without any global control, while guaranteeing the completeness of the algorithm. Furthermore, we describe how the asynchronous backtracking algorithm can be modified into a more efficient algorithm called an asynchronous weak-commitment search, which can revise a bad decision without exhaustive search by changing the priority order of agents dynamically. The experimental results on various example problems show that the asynchronous weak-commitment search algorithm is, by far more, efficient than the asynchronous backtracking algorithm and can solve fairly large-scale problems.
This article extends Simpson's (2003) research on sex differences in social dilemmas. To test the hypotheses that men defect in response to greed and women to fear, Simpson created Fear and Greed ...Dilemmas, but experiments using these games supported the greed hypothesis only. In this article I focus on why the fear hypothesis failed and suggest that fear was actually absent in the Fear Dilemma. To retest Simpson's hypotheses, I propose a new asymmetric game, the Fear-of-Greed Dilemma. The asymmetry is important for two reasons. First, it creates the risk of exploitation that Simpsons Fear Dilemma lacked. Second, it exposes a critical limitation in Rapoport's (1964) K-index and suggests a re-specification. Laboratory studies supported the fear hypothesis and found mediating effects of expectations about partners on sex differences in cooperation.
Background
In steroid‐naive patients with asthma, several gene variants are associated with a short‐term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in ...Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1) and the variant of the glucocorticoid‐induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long‐term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation.
Methods
In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single‐nucleotide polymorphisms (SNPs) in GLCCI1, stress‐induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined.
Results
Besides the known contributing factors, that is, the most intensive treatment step, ex‐smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group.
Conclusions
A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long‐term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.
Although accumulating evidence indicates that cAMP response element-binding protein (CREB) phosphorylation mediates not only synaptic plasticity but also survival of certain neurons, it remains ...uncertain whether CREB phosphorylation induced after metabolic insult leads to CRE-mediated gene transcription and is involved in cell survival or not. In the present study, we clarified that (1) CREB phosphorylation and ischemic tolerance induced after preconditioning ischemia in the hippocampal neurons was abolished by MK801 administration in gerbil global ischemia model, (2) CREB phosphorylation induced after exposure to glutamate in cultured neurons was inhibited by removal of extracellular calcium, by MK801 and by an inhibitor of calcium-calmodulin-dependent protein kinase (CaMK) II and IV, (3) inhibitor of CaMK II-IV or CRE-decoy oligonucleotide suppressed upregulation of BCL-2 expression and accelerated neuronal damage after exposure to glutamate, and (4) CREB phosphorylation induced in the hippocampal neurons after ischemia and in cultured neurons after exposure to glutamate was followed by CRE-mediated gene transcription in transgenic mice with a CRE-LacZ reporter. Our results suggest that CREB phosphorylation in neurons after ischemia and exposure to glutamate is induced by NMDA receptor-gated calcium influx and subsequent activation of CaMK II-IV and that CREB phosphorylation after metabolic stress might show a neuroprotective response through CRE-mediated gene induction.
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