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Bitter taste is sensed by bitter taste receptors (TAS2Rs) that belong to the G protein-coupled receptor (GPCR) superfamily. In addition to bitter taste perception, TAS2Rs have been reported recently to be expressed in many extraoral tissues and are now known to be involved in health and disease. Despite important roles of TAS2Rs in biological functions and diseases, no crystal structure is available to help understand the signal transduction mechanism or to help develop selective ligands as new therapeutic targets. We report here the three-dimensional structure of the fully activated TAS2R4 human bitter taste receptor predicted using the GEnSeMBLE complete sampling method. This TAS2R4 structure is coupled to the gustducin G protein and to each of several agonists. We find that the G protein couples to TAS2R4 by forming strong salt bridges to each of the three intracellular loops, orienting the activated Gα5 helix of the Gα subunit to interact extensively with the cytoplasmic region of the activated receptor. We find that the TAS2Rs exhibit unique motifs distinct from typical Class A GPCRs, leading to a distinct activation mechanism and a less stable inactive state. This fully activated bitter taste receptor complex structure provides insight into the signal transduction mechanism and into ligand binding to TAS2Rs.
We report the G protein-first mechanism for activation of G protein-coupled receptors (GPCR) for the three closest subtypes of the opioid receptors (OR), μOR, κOR and δOR. We find that they couple to the inactive Gi protein-bound guanosine diphosphate (GDP) prior to agonist binding. The inactive Gi protein forms anchors to the intracellular loops of the inactive apo-μOR, apo-κOR and apo-δOR, inducing opening of the cytoplasmic region to form a pre-activated state that holds Gi protein in place until agonist binds. Then, agonist binds to μOR, κOR and δOR already complexed with Gi protein, to trigger the Gαi to open up the tightly coupled GDP binding site, making GDP accessible for GTP exchange, an essential step for Gi signalling. We show that the agonist alone cannot open the intracellular region of μOR and κOR, requiring Gi protein to open the cytoplasmic region by itself. We consider that this G protein-first mechanism may apply to activation of other Class A GPCRs. However, for δOR, agonist binding can open up the intracellular region to encourage Gi protein recruitment. Thus, activation of Gi protein mediated by δOR favourably may proceed with either ligand-first or G protein-first activation mechanisms.
To examine the hypothesis that the association between vitamin D deficiency and depressive symptoms is dependent upon total cholesterol level in a representative national sample of the South Korean population.
This was a population-based cross-sectional study.
The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010–2012).
We included 7198 adults aged 20–88 years.
The incidence of depressive symptoms in individuals with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml) was 1·54-fold (95 % CI 1·20, 1·98) greater than in individuals without vitamin D deficiency (serum 25-hydroxyvitamin D ≥20 ng/ml). The relationship was stronger in individuals with normal-to-borderline serum total cholesterol (serum total cholesterol<240 mg/dl; OR=1·60; 95 % CI 1·23, 2·08) and non-significant in individuals with high serum total cholesterol (OR=0·97; 95 % CI 0·52, 1·81) after adjustment for confounding variables (age, sex, BMI, alcohol consumption, smoking status, regular exercise, income level, education level, marital status, changes in body weight, perceived body shape, season of examination date and cholesterol profiles).
The association between vitamin D deficiency and depressive symptoms was weakened by high serum total cholesterol status. These findings suggest that both vitamin D and total cholesterol are important targets for the prevention and treatment of depression.
We investigated whether dietary and urinary Na is associated with adiposity in Korean children and adolescents (10–18 years), a population with a high salt intake. Study subjects were Korean children and adolescents who participated in the cross-sectional nationally representative Korea National Health and Nutrition Examination Survey (2010–2011). This study used measures of dietary (24-h dietary recall) and urinary Na (Na:creatinine ratio) and three methods to determine obesity (BMI, waist circumference (WC) and total body per cent fat (TBPF)). Higher Na intake was significantly associated with obesity, adjusting for the covariates. Subjects in the highest tertile of urinary Na excretion had a significantly higher OR for higher adiposity compared with those in the lowest tertile (multivariate-adjusted OR 3·13 (95 % CI 1·81, 5·50) for BMI, 2·15 (95 % CI 1·27, 3·66) for WC and 1·92 (95 % CI 1·29, 2·86) for TBPF, respectively). Na intake estimated by the 24-h recall method also showed significant association with adiposity (multivariate-adjusted OR 2·79 (95 % CI 1·66, 4·68) for BMI and 2·14 (95 % CI 1·25, 3·67) for WC, respectively). The significant associations between Na and adiposity remained significant after additionally adjusting for sugar-sweetened beverage (SSB) consumption. Our results revealed a significant positive association between urinary and dietary Na and adiposity in Korean children and adolescents, independent of SSB consumption.
This study aimed to investigate the influences of age, education, and gender on the two total scores (TS-I and TS-II) of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological assessment battery (CERAD-NP) and to provide normative information based on an analysis for a large number of elderly persons with a wide range of educational levels.
In the study, 1,987 community-dwelling healthy volunteers (620 males and 1,367 females; 50–90 years of age; and zero to 25 years of education) were included. People with serious neurological, medical, and psychiatric disorders (including dementia) were excluded. All participants underwent the CERAD-NP assessment. TS-I was generated by summing raw scores from the CERAD-NP subtests, excluding Mini-Mental State Examination and Constructional Praxis (CP) recall subtests. TS-II was calculated by adding CP recall score to TS-I.
Both TS-I and TS-II were significantly influenced by demographic variables. Education accounted for the greatest proportion of score variance. Interaction effect between age and gender was found. Based on the results obtained, normative data of the CERAD-NP total scores were stratified by age (six overlapping tables), education (four strata), and gender.
The normative information will be very useful for better interpretation of the CERAD-NP total scores in various clinical and research settings and for comparing individuals’ performance of the battery across countries.
Although there are rapidly growing concerns about the high rates of cognitive dysfunction in Korea, the knowledge of risk factors for Alzheimer’s disease (AD) among the general public in Korea remains to be elucidated.
A total of 2767 randomly selected subjects from the Ansan Geriatric Study were questioned on their knowledge of putative risk factors for AD. Their answers were compared with their sociodemographic data and other variables.
The most common stated risk factor was being older (59.6%), followed by head trauma (33.6%) and cerebrovascular disease (30.4%). However, a substandard education, which is a known risk factor, was considered significant by only 9.5% of the subjects. Predictors for a worse knowledge of the risk factors for AD were being older, a lower level of education, lower economic status and the attitude that dementia is not curable.
This study revealed that misunderstanding about AD is more prevalent in older subjects and those with a lower level of education, and so public health education on the basic concepts of AD should be targeted at this population.
The prevalence of the feeling of cold hands and feet (FCHF) is high in the
general population but the etiology of FCHF is largely unknown. The aim of the
present study was to explore whether the FCHF is heritable. Eight hundred and
ninety-four pairs of twins completed a question about FCHF. Tetrachoric
correlations for FCHF were .58, .29, .67, .52, and .04 for monozygotic male,
dizygotic male, monozygotic female, and dizygotic female twins, respectively.
Model-fitting analyses suggested that in the best fitting model, additive
genetic and nonshared environmental variance including measurement error were
64% (95% CI: 55%-72%) and 36% (28%-45%), respectively. Sex differences in
genetic and environmental influences were not significant.
The Korean Twin Registry is the first nationwide twin study in Korea. We compiled 154,783 twin pairs from existing nationwide data sources, mainly from address and national health insurance data. The coverage of this registry was almost complete for the twins born since 1970, but less complete as age increased, so that there were only 990 pairs who were born before 1930. The twins' health examination (N = 54,390 persons) and questionnaire (N = 44,546 persons) results were incorporated into the registry, yielding 12,894 and 9074 concordantly informative pairs. Morbidity and mortality outcomes have been followed up since 1990, for most diseases. For preliminary analysis of complex diseases, we selected ventricular septal defects (VSD) in young twins, stomach and colorectal cancers in adult twins. We identified 353 VSDs, 284 stomach cancers, and 116 colorectal cancers among twins. The prevalence rates of cancers, but not that of VSD, were lower in twins than those in population. The difference in the cancer prevalence was marked for twins born before 1926, implying some degree of selection. Like-sex (LS) twins showed familial recurrence risks (λLS) of 41.2 for VSD and 22.4 for colorectal cancers, and 1.74 for stomach cancers. For opposite-sex (OS) twins, we could estimate λOS of 19.8 for VSD only. These results were compatible with previous studies for VSD and colorectal cancers, but not for stomach cancers. Despite the strength in size, availability of health outcomes, and some lifestyle and basic laboratory data, we need accurate zygosity information to improve the validity of the results.
We present a rapid and sensitive surface acoustic wave (SAW) immunosensor that utilizes gold staining as a signal enhancement method. A sandwich immunoassay was performed on sensing area of the SAW sensor, which could specifically capture and detect cardiac markers (cardiac troponin I (cTnI), creatine kinase (CK)-MB, and myoglobin). The analytes in human serum were captured on gold nanoparticles (AuNPs) that were conjugated in advance with detection antibodies. Introduction of these complexes to the capture antibody-immobilized sensor surface resulted in a classic AuNP-based sandwich immunoassay format that has been used for signal amplification. In order to achieve further signal enhancement, a gold staining method was performed, which demonstrated that it is possible to obtain gold staining-mediated signal augmentation on a mass-sensitive device. The sensor response due to gold staining varied as a function of cardiac marker concentration.
In this study, we synthesized ZnO nanowires using Au catalytic particles formed on a ZnO seed layer. We modulated the microstructure of the ZnO seed layer by changing the sputtering power to investigate how the underlying ZnO film microstructure affects the distribution of ZnO nanowires. Examining the samples after each of the three key steps of the growth process (ZnO seed layer deposition, Au catalytic particle formation, and nanowire growth) using various characterization methods such as scanning electron microscopy, transmission electron microscopy, and x-ray diffraction helped us illuminate the profound impacts of the grain size of the seed layer on the nanowire density.
The diatoms are an ecologically important group of algae that have been extensively studied by ecologists and taxonomists. However, the large-scale patterns of diatom distribution and the factors underlying this distribution are largely unknown. The aims of this study were to identify the large-scale spatial patterns of benthic diatom assemblages in Korean streams and rivers, and to assess the importance of numerous environmental factors on diatom distribution. We classified 720 study sites based on diatom flora. Benthic diatoms, water chemistry, altitude, and riparian land cover and use were characterized by multivariate analyses, Monte Carlo permutation tests, and indicator species analysis. In total, we identified 531 diatom taxa. Diatom assemblages were mostly dominated by species of the genera Achnanthes, Navicula, Nitzschia, Cocconeis, Fragilaria (Synedra included), Cymbella, Gomphonema, and Melosira. Cluster analysis partitioned all 720 sites into eight groups based on diatom species composition. Canonical correspondence analysis indicated that altitude, land cover and use, current velocity, electrical conductivity, and nutrient levels explained a significant amount of the variation in the composition of assemblages of benthic diatoms. At the national scale, a downstream ecological gradient was apparent, from fast-flowing, mostly oligotrophic highland streams to slow-flowing, mostly eutrophic lowland rivers. Our data suggest that spatial factors explain some of the variation in diatom distribution. The present investigation of the spatial patterns of benthic diatoms, the ecological determinants of diatom occurrence, and the identification of diatom indicator species contributes to development of a program for assessing the biological integrity of lotic ecosystems in Korea.
In this study, we assess the neuropsychological profiles of both early
and late symptom-onset obsessive-compulsive disorder (OCD) patients. The
early and late-onset OCD patients are compared to the control group with a
series of neuropsychological measurements. The late-onset OCD patients
exhibited impaired performance on the immediate and the delayed recall
conditions of the Rey-Osterrieth Complex Figure Test (RCFT) and the letter
and category fluency of the Controlled Oral Word Association Test (COWA),
compared to the normal controls and the early-onset OCD patients. The
controls and early-onset OCD patients did not differ on any of the
neuropsychological measurements taken in this study. These results suggest
that different neurophysiological mechanisms are in play in early and
late-onset OCD patients, and age of onset can serve as a potential marker
for the subtyping of OCD. (JINS, 2007, 13,
The aim of this study was to compare the effectiveness of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography (SPECT) and computed tomography (CT) in evaluating cervical lymph node metastasis of head and neck cancer. Histopathologic results of 166 cervical lymph node levels in 31 neck-dissected patients were compared with pre-operative CT and 99mTc-MIBI SPECT findings about cervical lymph node metastasis, retrospectively. Sensitivity, specificity and predictability of CT and 99mTc-MIBI SPECT were 68.2, 93.1 and 89.8 per cent and 59.1, 87.5 and 83.7 per cent, respectively. When analysing CT and99mTc-MIBI SPECT together, sensitivity and specificity were 86.4 and 99.3 per cent, respectively. The combined use of 99mTc-MIBI SPECT and CT could increase the accuracy of cervical lymph node metastases detection, compared with separate use of either 99mTc-MIBI SPECT or CT.
In this study we isolated a murine mAsb-17 from mouse testis by RT-PCR using primers designed based on the sequences from the GenBank database. The sequence analysis showed that mAsb-17 encodes a 295 amino acid polypeptide with a molecular weight of approximately 34 kDa containing two ankyrin repeats and one SOCS box. The amino acid sequence of mASB-17 showed 87.5%, 98.3% and 92.9% identity with that of human, rat and dog, respectively. Interestingly, northern blot analysis showed that mAsb-17 was expressed only in the testis. The expression analysis by RT-PCR for mAsb-17 in mouse indicates that mAsb-17 is expressed from the fourth week after birth to adult, with the highest expression in round spermatids. Both northern blot and RT-PCR analyses suggest that mASB-17 may play essential roles in testis development and spermatogenesis.
We have investigated the development of erbium(III)-cored supramolecular complexes containing metalloporphyrins to circumvent the solubility problem and improve the optical amplification property. The new synthetic methodology was accomplished through the ligand-exchange model reaction using ErCl3 to optimize its synthetic condition We have designed and synthesized the model complexes to investigate coordination property between the ligand and the erbium ion. Highly coordinated erbium(III)-cored model complexes (at least 8 to 10 coordination) showed the strong near infrared(IR) emission at 1520 nm, corresponding to the 4I13/2 → 4I15/2 transition. Also, with these synthetic results, erbium(III)-cored supramolecular complexes based on metalloporphyrins were synthesized and characterized. They also showed the infrared emission of the 4I13/2 → 4I15/2 transition at 1520 nm.
In this study, we have investigated microencapsulation of magenta, yellow, and cyan color polymer balls with white pigment for multi-color electrophoretic display implementation. The charged color pigments have been prepared by physical coating of magenta, yellow, and cyan with functionalized polymers, then surface charging with charge control agent. These color balls with white pigment were microencapsulated in suspending fluid through in-situ polymerization.
We have investigated the growth mechanism and thin film morphology of pentacene thin films by the process of low-pressure gas assisted organic vapor deposition (LP-GAOVD). As the source temperature, flow rate of the carrier gas, substrate temperature and chamber pressure were varied, the growth rate, morphology and grain size of the films were differently obtained. The electrical properties of pentacene thin films for applications in organic thin film transistor and electrophoretic displays were discussed
Telomerase maintains the length of telomeres in immortal cells and is also often associated with cell proliferation. Cholesteatoma epithelium is characterized by a dysregulation with hyperproliferative growth. The study evaluated the telomerase activity in cholesteatoma and normal retro-auricular skin to discover the relationship between telomerase expression and clinical findings. Twenty-two samples of cholesteatoma and 15 samples of retro-auricular skin were obtained from patients undergoing middle-ear surgery. The telomerase activity was detected by the telomerase repeat amplification protocol (TRAP) assay method. Seventeen of the 22 (77.3 per cent) cholesteatoma cases expressed telomerase activity, whereas none of the 15 retro-auricular normal skin (0 per cent) detected telomerase activity. There was no significant difference between telomerase expressions and clinical findings, including hearing level, duration of disease, and the degree of extension (p>0.05). The high expression of telomerase in cholesteatoma suggests that the activation of telomerase may be related to the proliferative nature of cholesteatoma.
In a metastable solution the particle growth rate of silicon dioxide increased with an increase in the initial supersaturation of the metastable solution and agitation speed in the ranges of 2.5 × 10−4 to 2.0 × 10−3 M and 300–1500 rpm, respectively. Based on a power law expression, the particle growth rate order was estimated as 2.0 independent of the initial supersaturation and agitation speed. Meanwhile, the particle growth rate coefficient was enhanced from 2.0 × 10−3 to 1.4 × 10−2 with increase in the agitation speed from 300 to 1500 rpm. From the experimental data, it would appear that the enhanced particle growth rate resulted from the promotion of molecular transport due to the agitation and driving force of the supersaturation in the particle growth process. A slight addition of sodium chloride into the metastable solution caused a marked reduction of the particle growth rate due to the inhibition of growth process by sodium chloride adsorbed on the particle. This effect of sodium chloride on the particle growth appeared in a significant drop of the particle growth rate coefficient from 4.5 × 10−3 to 8.0×10−4 with increase in the sodium chloride concentration from zero to 5.0×10−3 M, but not in the particle growth rate order. The influence of sodium chloride on the particle growth process of silicon dioxide predicted with a Langmuir isotherm matched with the experimental data.