Environmental risk score of multiple pollutants for kidney damage among residents in vulnerable areas by occupational chemical exposure in Korea.

This study aimed to develop an environmental risk score (ERS) of multiple pollutants (MP) causing kidney damage (KD) in Korean residents near abandoned metal mines or smelters and evaluate the association between ERS and KD by a history of occupational chemical exposure (OCE). Exposure to MP, consisting of nine metals, four polycyclic aromatic hydrocarbons, and four volatile organic compounds, was measured as urinary metabolites. The study participants were recruited from the Forensic Research via Omics Markers (FROM) study (n = 256). Beta-2-microglobulin (ß2-MG), N-acetyl-ß-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) were used as biomarkers of KD. Bayesian kernel machine regression (BKMR) was selected as the optimal ERS model with the best performance and stability of the predicted effect size among the elastic net, adaptive elastic net, weighted quantile sum regression, BKMR, Bayesian additive regression tree, and super learner model. Variable importance was estimated to evaluate the effects of metabolites on KD. When stratified with the history of OCE after adjusting for several confounding factors, the risks for KD were higher in the OCE group than those in the non-OCE group; the odds ratio (OR; 95% CI) for ERS in non-OCE and OCE groups were 2.97 (2.19, 4.02) and 6.43 (2.85, 14.5) for ß2-MG, 1.37 (1.01, 1.86) and 4.16 (1.85, 9.39) for NAG, and 4.57 (3.37, 6.19) and 6.44 (2.85, 14.5) for eGFR, respectively. We found that the ERS stratified history of OCE was the most suitable for evaluating the association between MP and KD, and the risks were higher in the OCE group than those in the non-OCE group.

Associations between plasma metabolites and heavy metal exposure in residents of environmentally polluted areas.

Heavy metals are commonly released into the environment through industrial processes such as mining and refining. The rapid industrialization that occurred in South Korea during the 1960s and 1970s contributed significantly to the economy of the country; however, the associated mining and refining led to considerable environmental pollution, and although mining is now in decline in South Korea, the detrimental effects on residents inhabiting the surrounding areas remain. The bioaccumulation of toxic heavy metals leads to metabolic alterations in human homeostasis, with disruptions in this balance leading to various health issues. This study used metabolomics to explore metabolomic alterations in the plasma samples of residents living in mining and refining areas. The results showed significant increases in metabolites involved in glycolysis and the surrounding metabolic pathways, such as glucose-6-phosphate, phosphoenolpyruvate, lactate, and inosine monophosphate, in those inhabiting polluted areas. An investigation of the associations between metabolites and blood clinical parameters through meet-in-the-middle analysis indicated that female residents were more affected by heavy metal exposure, resulting in more metabolomic alterations. For women, inhabiting the abandoned mine area, metabolites in the glycolysis and pentose phosphate pathways, such as ribose-5-phosphate and 3-phosphoglycerate, have shown a negative correlation with albumin and calcium. Finally, Mendelian randomization(MR) was used to determine the causal effects of these heavy metal exposure-related metabolites on heavy metal exposure-related clinical parameters. Metabolite biomarkers could provide insights into altered metabolic pathways related to exposure to toxic heavy metals and improve our understanding of the molecular mechanisms underlying the health effects of toxic heavy metal exposure.

Uncovering the health implications of abandoned mines through protein profiling of local residents.

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia.

Relationship of bisphenol A substitutes bisphenol F and bisphenol S with adiponectin/leptin ratio among children from the environment and development of children cohort.

BACKGROUND: Bisphenol A (BPA) is known as an obesogenic endocrine disruptor. Bisphenol S (BPS) and F (BPF) are substitutes that have recently replaced BPA. OBJECTIVES: To investigate the relationships of urinary bisphenols (BPA, BPS and BPF) with adiposity measurements (obesity, BMI z-score, and fat mass), serum adipokine levels (adiponectin and leptin), and adiponectin/leptin ratio (A/L ratio) in 6- and 8-year-old children. METHODS: A total of 561 children who participated in the Environment and Development of Children cohort (482 and 516 children visited at age 6 and 8, respectively) at Seoul National University Children's Hospital during 2015-2019 were included. Urinary BPA levels were log-transformed. BPS levels were categorized into three groups (non-detected, lower-half, and higher-half of detected), and BPF levels were classified into two groups (non-detected and detected). RESULTS: The urinary BPS higher-half group had a higher BMI z-score (ß = 0.160, P= 0.044), higher fat mass (ß = 0.104, P< 0.001), lower adiponectin concentration (ß =- 0.069, P< 0.001), higher leptin concentration (ß = 0.360, P< 0.001), and lower A/L ratio (ß =- 0.428, P< 0.001) compared with the non-detected group. The urinary BPF-detected group had a higher fat mass (ß = 0.074, P< 0.001), lower adiponectin concentration (ß =- 0.069, P< 0.001), higher leptin concentration (ß = 0.360, P< 0.001), and lower A/L ratio (ß =- 0.428, P< 0.001) compared with the non-detected group. The BPA levels showed no consistent associations with outcomes, except for isolated associations of BPA at age 6 with a higher BMI z-score at age 6 (P= 0.016) and leptin at age 8 (P= 0.021). CONCLUSIONS: Increased exposure to BPS and BPF is associated with higher fat mass and leptin concentration, lower serum adiponectin, and lower A/L ratio in children. These findings suggest potential adverse effects of BPA substitutes on adiposity and adipokines. No consistent association of BPA exposure with outcomes could be partly explained by the decreasing BPA levels over time.

Cadmium-associated protein changes in residents of contaminated areas: Abandoned mine and smelter.

Cadmium (Cd), a serious environmental contaminant, is associated with adverse health effects. However, the specific changes that the human body experiences in response to exposure to varying concentrations of cadmium remain unknown. The high levels of heavy metal contamination, especially Cd, in abandoned mines and smelter sites make them ideal locations to investigate the physiological manifestations of Cd exposure. This study found that individuals inhabiting abandoned mine and smelter areas had higher concentrations of Cd in their urine and blood compared to those living outside these areas (i.e., the controls). Furthermore, proteomic profiling of blood samples from all study groups was performed to identify proteomic biomarkers associated with chronic and severe Cd exposure. This analysis showed statistically significant correlations between urine Cd levels and sixteen proteins. Among these proteins, seven exhibited significantly altered expressions in samples from contaminated areas compared with those from control areas. Therefore, these proteins were selected as potential markers representing Cd-related protein alterations. Multiple reaction monitoring analysis was performed to validate the expression patterns of the proteins and four proteins were found to exhibit consistent trends. The findings show that Cd exposure significantly affects the expression of certain proteins in the human body. Understanding the underlying mechanisms and diseases associated with Cd-induced protein alterations can aid in the development of effective preventive and therapeutic strategies for individuals exposed to Cd-linked pollution.

Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas.

Abandoned metal mines and refineries are considered environmentally vulnerable areas owing to high levels of exposure to heavy metals. This study examined the association between heavy metal exposure and renal function indicators. We studied a total of 298 participants, of which 74 and 68 resided in low- and high-exposure abandoned metal mine areas, respectively, with 121 in the refinery area and 35 in the control area. Blood and urine samples were collected from the participants to analyze the levels of blood lead, cadmium, and creatinine and urinary cadmium, NAG, and ß2-MG. The estimated glomerular filtration rate, which is calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, was used for assessments. The study participants comprised more females than males, and their mean age was 70.3 years. The blood lead and cadmium as well as urinary cadmium levels were 2.12 µg/dL, 1.89 µg/L, and 2.11 µg/L, respectively, in the heavy metal-exposure areas, and 1.18 µg/dL, 0.89 µg/L, and 1.11 µg/L, respectively, in the control area. The odds ratio (OR) for exceeding the reference value showed that blood cadmium in the refinery area was 38 times higher than that in the control area. Urinary cadmium was seven times higher in the low-exposure abandoned metal mine area than in the control area. NAG showed a positive correlation with urinary cadmium in all areas. In the refinery area, correlations were observed between ß2-MG and urinary cadmium levels and the eGFR and blood cadmium level; in the high-exposure abandoned metal mine area, correlations were observed between NAG, ß2-MG, and the eGFR and blood cadmium. In this study, the association between Cd exposure and some renal function indicators was observed. This study's findings and the obtained biological samples can serve as a basis for future molecular biological research.

Relationship between bisphenol A, bisphenol S, and bisphenol F and serum uric acid concentrations among school-aged children.

BACKGROUND: Hyperuricemia has a suspected relationship with hypertension, metabolic syndrome, kidney disease, and cardiovascular disease. Endocrine disruptors may affect uric acid metabolism; however, few epidemiologic studies have been performed in children regarding newly developed bisphenol A (BPA) substitutes. We evaluated the associations between BPA, bisphenol S (BPS), and bisphenol F (BPF) exposure and serum uric acid concentrations in 6-year-old Korean children. METHODS: From the Environment and Development of Children cohort study, six-year-old children (N = 489; 251 boys) who underwent an examination during 2015-2017 were included. Anthropometry, questionnaires, and biological samples were evaluated. BPA, BPS, and BPF levels were measured from spot urine samples, and log-transformed or categorized into groups for analysis. We constructed linear regression models adjusting for age, sex, urinary creatinine levels, body mass index z-scores, and estimated glomerular filtration rates. RESULTS: Mean serum uric level was 4.2 mg dL-1 (0.8 SD) without sex-differences. Among the three bisphenols, higher BPS exposure was associated with increased serum uric acid concentrations (P-value for trend = 0.002). When BPS levels were categorized into three groups (non-detection < 0.02 µg L-1 vs. medium BPS; 0.02-0.05 µg L-1 vs. high BPS ≥ 0.05 µg L-1), the high BPS group showed higher serum uric acid concentrations (by 0.26 mg dL-1, P = 0.003) than the non-detection group after adjusting for covariates, which was significant in boys but not girls. DISCUSSIONS: Urinary BPS levels was positively associated with serum uric acid concentrations in 6-year-old children, and the association was more pronounced in boys. Considering the increasing use of BPS and concerning effect of hyperuricemia on health outcomes, their positive relationship should be investigated further.

The current status of studies of human exposure assessment of microplastics and their health effects: a rapid systematic review.

This rapid systematic review aims to summarize studies of human exposure to microplastics (MPs) and their health effects. For the systematic literature review, we separately searched for review articles and original articles published from 2000 to 2019 in the PubMed, NDSL, KMBASE, and Cochrane databases. A total of 276 review articles and 475 original articles were independently evaluated and eligibility of each article was assessed by two researchers. Finally, 8 review articles and 13 original articles were selected for analysis. There was no standardized methodology for determining human exposure to MPs. Therefore, the size, shape, color, and chemical composition of MPs were considered as factors that affected human exposure to MP. We ascertained that human exposure to MPs occurs through two major routes: inhalation and ingestion. The general population can be exposed to MPs through the food chain, food, and mineral water. Thus, there are multiple scenarios for the exposure process. The only exposure marker in humans is the detection and measurement of MPs in feces. Health effects of human exposure to MPs include respiratory effects from inhalation, digestive effects from ingestion, oxidative stress, and cancer. However, there are few studies of the effects of MP exposure in the general population. Based on a systematic review, we propose a standardized methodology to identify various exposure scenarios to facilitate studies of human exposure to MPs and their health effects.

Identification of Monoallelically Expressed Genes Associated with Economic Traits in Hanwoo (Korean Native Cattle).

Hanwoo, an indigenous Korean cattle breed, has been genetically improved by selecting superior sires called Korean-proven bulls. However, cows still contribute half of the genetic stock of their offspring, and allelic-specific expressed genes have potential, as selective targets of cows, to enhance genetic gain. The aim of this study is to identify genes that have MAEs based on both the genome and transcriptome and to estimate their effects on breeding values (BVs) for economically important traits in Hanwoo. We generated resequencing data for the parents and RNA-sequencing data for the muscle, fat, and brain tissues of the offspring. A total of 3801 heterozygous single nucleotide polymorphisms (SNPs) in offspring were identified and they were located in 1569 genes. Only 14 genes showed MAE (seven expressing maternal alleles and seven expressing paternal alleles). Tissue-specific MAE was observed, and LANCL1 showed maternal allele expression across all tissues. MAE genes were enriched for the biological process of cell death and angiogenesis, which included ACKR3 and PDCL3 genes, whose SNPs were significantly associated with BVs of lean meat production-related traits, such as weight at 12 months of age, carcass weight, and loin eye area. In the current study, monoallelically expressed genes were identified in various adult tissues and these genes were associated with genetic capacity in Hanwoo.

Trends in the Prevalence of Childhood Asthma in Seoul Metropolitan City, Korea: The Seoul Atopy ∙ Asthma-friendly School Project.

OBJECTIVES: The project Seoul Atopy ∙ Asthma-friendly School investigated the current status of childhood asthma to enable formulation of a preventative policy. We evaluated the current prevalence of childhood asthma in Seoul and its trends and related factors. METHODS: The project was conducted annually from 2011 to 2016 and involved around 35 000 children aged 1-13 years. Based on the International Study of Asthma and Allergies in Childhood guidelines, the survey involved parents. The associations of the particulate matter (PM10) concentration, and the number of days on which the daily air quality guidance level was exceeded in the 25 districts of Seoul, with the prevalence of asthma were assessed. RESULTS: The age-standardized asthma prevalence in 2011 and 2016 was 6.74 and 4.02%, respectively. The prevalence of lifetime asthma treatment and treatment during the last 12 months tended to decrease from 2011 to 2016. Asthma treatment was significantly correlated with the number of days on which the daily air quality guidance level was exceeded, but not with the PM10 concentration. CONCLUSIONS: This study reports the prevalence of asthma among children in Seoul and confirmed the relationship between childhood asthma and known risk factors in a large-scale survey.

Accuracy of Imputation of Microsatellite Markers from BovineSNP50 and BovineHD BeadChip in Hanwoo Population of Korea.

Until now microsatellite (MS) have been a popular choice of markers for parentage verification. Recently many countries have moved or are in process of moving from MS markers to single nucleotide polymorphism (SNP) markers for parentage testing. FAO-ISAG has also come up with a panel of 200 SNPs to replace the use of MS markers in parentage verification. However, in many countries most of the animals were genotyped by MS markers till now and the sudden shift to SNP markers will render the data of those animals useless. As National Institute of Animal Science in South Korea plans to move from standard ISAG recommended MS markers to SNPs, it faces the dilemma of exclusion of old animals that were genotyped by MS markers. Thus to facilitate this shift from MS to SNPs, such that the existing animals with MS data could still be used for parentage verification, this study was performed. In the current study we performed imputation of MS markers from the SNPs in the 500-kb region of the MS marker on either side. This method will provide an easy option for the labs to combine the data from the old and the current set of animals. It will be a cost efficient replacement of genotyping with the additional markers. We used 1,480 Hanwoo animals with both the MS data and SNP data to impute in the validation animals. We also compared the imputation accuracy between BovineSNP50 and BovineHD BeadChip. In our study the genotype concordance of 40% and 43% was observed in the BovineSNP50 and BovineHD BeadChip respectively.

Artificial selection increased body weight but induced increase of runs of homozygosity in Hanwoo cattle.

Artificial selection has been demonstrated to have a rapid and significant effect on the phenotype and genome of an organism. However, most previous studies on artificial selection have focused solely on genomic sequences modified by artificial selection or genomic sequences associated with a specific trait. In this study, we generated whole genome sequencing data of 126 cattle under artificial selection, and 24,973,862 single nucleotide variants to investigate the relationship among artificial selection, genomic sequences and trait. Using runs of homozygosity detected by the variants, we showed increase of inbreeding for decades, and at the same time demonstrated a little influence of recent inbreeding on body weight. Also, we could identify ~0.2 Mb runs of homozygosity segment which may be created by recent artificial selection. This approach may aid in development of genetic markers directly influenced by artificial selection, and provide insight into the process of artificial selection.

Fish consumption, mercury exposure, and the risk of cholesterol profiles: findings from the Korea National Health and Nutrition Examination Survey 2010-2011.

In this study, the associations between mercury (Hg) exposure and cholesterol profiles were analyzed, and increased Hg levels and cholesterol profiles according to the amount of fish consumption were evaluated. Data on levels of blood Hg, the frequency of fish consumption, total blood cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) in 3951 adults were obtained from the Korea National Health and Nutrition Examination Survey 2010-2011 database. To compare the distribution for each log-transformed indicator, Student's t-test and analysis of variance were carried out, and the groups were classified according to the frequency of fish consumption through linear regression analysis; the association between Hg level and cholesterol profiles in each group was analyzed. The blood Hg levels (arithmetic mean, median, and geometric mean) for all target participants were 4.59, 3.66, and 3.74 µg/L, respectively. The high cholesterol group, low HDL-C group, and high TG group showed a statistically and significantly higher blood Hg level than the low-risk group. In both sexes, as the frequency of fish consumption increased, blood Hg level also increased, but TC, HDL-C, LDL-C, and TG did not show a similar trend. Increased blood Hg level showed a significant association with increased TC and LDL-C. This statistical significance was maintained in the group with less frequent fish consumption (<4 times per month), but the group with frequent fish consumption (>8 times per month) did not show a similar trend. The results of this study suggest that fish consumption increases the level of Hg exposure, and that as the level of Hg exposure increases, the levels of cholesterol profiles increase. However, this study also suggests that the levels of cholesterol profiles in those with frequent fish consumption can be diminished.

Identification of the acclimation genes in transcriptomic responses to heat stress of White Pekin duck.

White Pekin duck is an important meat resource in the livestock industries. However, the temperature increase due to global warming has become a serious environmental factor in duck production, because of hyperthermia. Therefore, identifying the gene regulations and understanding the molecular mechanism for adaptation to the warmer environment will provide insightful information on the acclimation system of ducks. This study examined transcriptomic responses to heat stress treatments (3 and 6 h at 35 °C) and control (C, 25 °C) using RNA-sequencing analysis of genes from the breast muscle tissue. Based on three distinct differentially expressed gene (DEG) sets (3H/C, 6H/C, and 6H/3H), the expression patterns of significant DEGs (absolute log2 > 1.0 and false discovery rate < 0.05) were clustered into three responsive gene groups divided into upregulated and downregulated genes. Next, we analyzed the clusters that showed relatively higher expression levels in 3H/C and lower levels in 6H/C with much lower or opposite levels in 6H/3H; we referred to these clusters as the adaptable responsive gene group. These genes were significantly enriched in the ErbB signaling pathway, neuroactive ligand-receptor interaction and type II diabetes mellitus in the KEGG pathways (P < 0.01). From the functional enrichment analysis and significantly regulated genes observed in the enriched pathways, we think that the adaptable responsive genes are responsible for the acclimation mechanism of ducks and suggest that the regulation of phosphoinositide 3-kinase genes including PIK3R6, PIK3R5, and PIK3C2B has an important relationship with the mechanisms of adaptation to heat stress in ducks.

A cross-sectional study of the association between mobile phone use and symptoms of ill health.

OBJECTIVES: This study analyzed the associations between mobile phone call frequency and duration with non-specific symptoms. METHODS: This study was conducted with a population group including 532 non-patient adults established by the Korean Genome and Epidemiology Study. The pattern of phone call using a mobile phone was investigated through face-to-face interview. Structured methods applied to quantitatively assess health effects are Headache Impact Test-6 (HIT-6), Psychosocial Well-being Index-Short Form, Beck Depression Inventory, Korean-Instrumental Activities of Daily Living, Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index, and 12-item Short Form Health Survey where a higher score represents a higher greater health effect. RESULTS: The average daily phone call frequency showed a significant correlation with the PSS score in female subjects. Increases in the average duration of one phone call were significantly correlated with increases in the severity of headaches in both sexes. The mean (standard deviation) HIT-6 score in the subgroup of subjects whose average duration of one phone call was five minutes or longer was 45.98 (8.15), as compared with 42.48 (7.20) in those whose average duration of one phone call was <5 minutes. The severity of headaches was divided into three levels according to the HIT-6 score (little or no impact/moderate impact/substantial or severe impact), and a logistic regression analysis was performed to investigate the association between an increased phone call duration and the headache severity. When the average duration of one phone call was five minutes or longer, the odds ratio (ORs) and the 95% confidence intervals (CIs) for the moderate impact group were 2.22 and 1.18 to 4.19, respectively. The OR and 95% CI for the substantial or severe impact group were 4.44 and 2.11 to 8.90, respectively. CONCLUSIONS: Mobile phone call duration was not significantly associated with stress, sleep, cognitive function, or depression, but was associated with the severity of headaches.

Evolutionary Analyses of Hanwoo (Korean Cattle)-Specific Single-Nucleotide Polymorphisms and Genes Using Whole-Genome Resequencing Data of a Hanwoo Population.

Advances in next generation sequencing (NGS) technologies have enabled population-level studies for many animals to unravel the relationships between genotypic differences and traits of specific populations. The objective of this study was to perform evolutionary analysis of single nucleotide polymorphisms (SNP) in genes of Korean native cattle Hanwoo in comparison to SNP data from four other cattle breeds (Jersey, Simmental, Angus, and Holstein) and four related species (pig, horse, human, and mouse) obtained from public databases through NGS-based resequencing. We analyzed population structures and differentiation levels for the five cattle breeds and estimated species-specific SNPs with their origins and phylogenetic relationships among species. In addition, we identified Hanwoo-specific genes and proteins, and determined distinct changes in protein-protein interactions among five species (cattle, pig, horse, human, mouse) in the STRING network database by additionally considering indirect protein interactions. We found that the Hanwoo population was clearly different from the other four cattle populations. There were Hanwoo-specific genes related to its meat trait. Protein interaction rewiring analysis also confirmed that there were Hanwoo-specific protein-protein interactions that might have contributed to its unique meat quality.

Design of anti-BVDV drug based on common chemical features, their interaction, and scaffolds of TLR8 agonists.

In the absence of an experimental bTLR8 structure, recent studies have called attention to the fact that bTLR8 can also be activated by hTLR7/hTLR8 agonist, such as antiviral imidazoquinoline derivatives of resiquimod (R848) and imiquimod (R837) as well as some guanine nucleotide analogs with a scaffold structure related to the nucleic acids of ssRNA virus. In particular, the known small agonists (namely CL075, CL097 and R848) have been targeted to determine distinguishable deciding factors in complex with dimeric bTLR8-ECDs in comparison to ligand-induced activated hTLR8-ECDs. According to basic knowledge, the deciding eligibility criteria can be subsequently applied in our bTLR8 model to characterize the 3D-arrangement of chemical features (pharmacophore) and to investigate the distinct restrictions affecting species-specificity on dual TLR7/TLR8 small agonists suggested in previous works. Despite the lack of extensive structural biology studies regarding the interaction of bTLR8-ECDs with the agonists, our complex models of bTLR8-ECDs and the known agonists were applied to identify the deciding factors required for the interactions from agonist-based and (bTLR8-agonist complexes) structure-based pharmacophores. These pharmacophore constraints impose their essential chemical features to active bTLR8 receptors. The characterized pharmacophores all were employed in the virtual screening of candidates with a further acting factor of calf immune enhancer. Two hits were suggested as satisfying all decision factors to identify a potent bTLR8-specific agent with novel scaffolds dissimilar to imidazoquinoline analogues lacking overall homogeneity.

Analysis of extended haplotype in Korean cattle (Hanwoo) population.

Korean cattle (Hanwoo) are categorized into three breeds based on color: brown, brindle, and black. Among these breeds, brown Hanwoo has been subjected to intensive selection to improve meat traits. To identify genetic traces driven by recent selection in brown Hanwoo, we scanned the genomes of brown and brindle Hanwoo using a bovine SNP chip. We identified 17 candidate selection signatures in brown Hanwoo and sequenced four candidate regions from 10 individuals each of brown and brindle Hanwoo. In particular, non-synonymous SNPs in the ADSL gene (K88M, L189H, and R302Q) might have had mutational effects on protein structure as a result of altering the purine pathway during nucleotide breakdown. The ADSL gene was previously reported to affect meat quality and yield in livestock. Meat quality and yield are main breeding goals for brown Hanwoo, and our results support a potential causal influence of non-synonymous SNPs in the ADSL gene. [BMB Reports 2016; 49(9): 514-519].

Copy number variations in Hanwoo and Yanbian cattle genomes using the massively parallel sequencing data.

Hanwoo is an indigenous Korean beef cattle breed, and it shared an ancestor with Yanbian cattle that are found in the Northeast provinces in China until the last century. During recent decades, those cattle breeds experienced different selection pressures. Here, we present genome-wide copy number variations (CNVs) by comparing Hanwoo and Yanbian cattle sequencing data. We used ~3.12 and ~3.07 billion sequence reads from Hanwoo and Yanbian cattle, respectively. A total of 901 putative CNV regions (CNVRs) were identified throughout the genome, representing 5,513,340bp. This is a smaller number than has been reported in previous studies, indicating that Hanwoo are genetically close to Yanbian cattle. Of the CNVRs, 53.2% and 46.8% were found to be gains and losses in Hanwoo. Potential functional roles of each CNVR were assessed by annotating all CNVRs and gene ontology (GO) enrichment analysis. We found that 278 CNVRs overlapped with cattle gene-sets (genic-CNVRs) that could be promising candidates to account for economically important traits in cattle. The enrichment analysis indicated that genes were significantly over-represented in GO terms, including developmental process, multicellular organismal process, reproduction, and response to stimulus. These results provide a valuable genomic resource for determining how CNVs are associated with cattle traits.