Jeonghyun Kim

The PARK2 gene is involved in the maintenance of pancreatic β-cell functions related to insulin production and secretion.

Several association studies have implicated the PARK2 gene that encodes parkin--the key molecule orchestrating the mitochondrial quality control system--as a candidate susceptibility gene for diabetes. A total of 7551 unrelated Korean KARE cohort subjects were analyzed to investigate the association between the PARK2 single nucleotide polymorphism (SNP) and quantitative glycemic traits. Two SNPs, rs10455889 and rs9365294, were significantly associated with fasting plasma glucose level (p=∼1.2×10(-4)) and insulin secretion indices (p=∼7.4×10(-5)) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 β-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted β-cells also exhibited increased mitochondrial fragmentation and ROS production and decreased mitochondrial membrane potential. Both population-based statistical evaluation and experimental evidence demonstrated a fundamental role of the PARK2 gene in the maintenance of β-cell function.

Caloric restriction improves diabetes-induced cognitive deficits by attenuating neurogranin-associated calcium signaling in high-fat diet-fed mice.

Diabetes-induced cognitive decline has been recognized in human patients of type 2 diabetes mellitus and mouse model of obesity, but the underlying mechanisms or therapeutic targets are not clearly identified. We investigated the effect of caloric restriction on diabetes-induced memory deficits and searched a molecular mechanism of caloric restriction-mediated neuroprotection. C57BL/6 mice were fed a high-fat diet for 40 weeks and RNA-seq analysis was performed in the hippocampus of high-fat diet-fed mice. To investigate caloric restriction effect on differential expression of genes, mice were fed high-fat diet for 20 weeks and continued on high-fat diet or subjected to caloric restriction (2 g/day) for 12 weeks. High-fat diet-fed mice exhibited insulin resistance, glial activation, blood–brain barrier leakage, and memory deficits, in that we identified neurogranin, a down-regulated gene in high-fat diet-fed mice using RNA-seq analysis; neurogranin regulates Ca2+/calmodulin-dependent synaptic function. Caloric restriction increased insulin sensitivity, reduced high-fat diet-induced blood–brain barrier leakage and glial activation, and improved memory deficit. Furthermore, caloric restriction reversed high-fat diet-induced expression of neurogranin and the activation of Ca2+/calmodulin-dependent protein kinase II and calpain as well as the downstream effectors. Our results suggest that neurogranin is an important factor of high-fat diet-induced memory deficits on which caloric restriction has a therapeutic effect by regulating neurogranin-associated calcium signaling.

Development of a 3D Underground Cadastral System with Indoor Mapping for As-Built BIM: The Case Study of Gangnam Subway Station in Korea.

The cadastral system provides land ownership information by registering and representing land boundaries on a map. The current cadastral system in Korea, however, focuses mainly on the management of 2D land-surface boundaries. It is not yet possible to provide efficient or reliable land administration, as this 2D system cannot support or manage land information on 3D properties (including architectures and civil infrastructures) for both above-ground and underground facilities. A geometrical model of the 3D parcel, therefore, is required for registration of 3D properties. This paper, considering the role of the cadastral system, proposes a framework for a 3D underground cadastral system that can register various types of 3D underground properties using indoor mapping for as-built Building Information Modeling (BIM). The implementation consists of four phases: (1) geometric modeling of a real underground infrastructure using terrestrial laser scanning data; (2) implementation of as-built BIM based on geometric modeling results; (3) accuracy assessment for created as-built BIM using reference points acquired by total station; and (4) creation of three types of 3D underground cadastral map to represent underground properties. The experimental results, based on indoor mapping for as-built BIM, show that the proposed framework for a 3D underground cadastral system is able to register the rights, responsibilities, and restrictions corresponding to the 3D underground properties. In this way, clearly identifying the underground physical situation enables more reliable and effective decision-making in all aspects of the national land administration system.

Association of the I264T variant in the sulfide quinone reductase-like (SQRDL) gene with osteoporosis in Korean postmenopausal women.

To identify novel susceptibility variants for osteoporosis in Korean postmenopausal women, we performed a genome-wide association analysis of 1180 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 405 individuals with osteoporosis and 722 normal controls of the Korean Association Resource cohort. A logistic regression analysis revealed 72 nsSNPs that showed a significant association with osteoporosis (p<0.05). The top 10 nsSNPs showing the lowest p-values (p = 5.2×10-4–8.5×10-3) were further studied to investigate their effects at the protein level. Based on the results of an in silico prediction of the protein’s functional effect based on amino acid alterations and a sequence conservation evaluation of the amino acid residues at the positions of the nsSNPs among orthologues, we selected one nsSNP in the SQRDL gene (rs1044032, SQRDL I264T) as a meaningful genetic variant associated with postmenopausal osteoporosis. To assess whether the SQRDL I264T variant played a functional role in the pathogenesis of osteoporosis, we examined the in vitro effect of the nsSNP on bone remodeling. Overexpression of the SQRDL I264T variant in the preosteoblast MC3T3-E1 cells significantly increased alkaline phosphatase activity, mineralization, and the mRNA expression of osteoblastogenesis markers, Runx2, Sp7, and Bglap genes, whereas the SQRDL wild type had no effect or a negative effect on osteoblast differentiation. Overexpression of the SQRDL I264T variant did not affect osteoclast differentiation of the primary-cultured monocytes. The known effects of hydrogen sulfide (H2S) on bone remodeling may explain the findings of the current study, which demonstrated the functional role of the H2S-catalyzing enzyme SQRDL I264T variant in osteoblast differentiation. In conclusion, the results of the statistical and experimental analyses indicate that the SQRDL I264T nsSNP may be a significant susceptibility variant for osteoporosis in Korean postmenopausal women that is involved in osteoblast differentiation.

The effect of Lycii Radicis Cortex extract on bone formation in vitro and in vivo.

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for their ability to increase the cellular proliferation and differentiation of two osteoblastic cell lines: C3H10T1/2 and MC3T3-E1. We selected a Lycii Radicis Cortex (LRC), Lycium Chinese root bark as the primary candidate. Treatment with LRC extract showed enhanced alkaline phosphatase activity and increased expression of bone metabolic markers Alpl, Runx2, and Bglap genes in both osteoblastic cell lines. There was no effect on the osteoclastic differentiation of primary-cultured monocytes from the mouse bone marrows. Furthermore, the study examined the effect of LRC extract in vivo in ovariectomizd (OVX) mice for 8 weeks and 16 weeks, respectively. Bone mineral density (BMD) was significantly higher in LRC extract-administered group than in the non-LRC-administered OVX control group. The results indicated that LRC extract prevented the OVX-induced BMD loss in mice via promoting the differentiation of osteoblast linage cells. These results suggest that LRC extract may be a good natural herbal medicine candidate for the treatment of osteoporosis.

Association between the SPRY1 gene polymorphism and obesity-related traits and osteoporosis in Korean women

BACKGROUND Emerging evidence has revealed a close relationship between obesity and osteoporosis. It was reported recently that conditional knockout of the Spry1 gene in mice adipocytes causes an increase in body fat and a decrease in bone mass, and that these phenotypes are rescued by Spry1 overexpression in adipose tissue. In this study, we investigated whether genetic variation in the human SPRY1 gene is associated with obesity-related phenotypes and/or osteoporosis in humans. METHODS We performed a candidate gene association analysis between the four single nucleotide polymorphisms (SNPs) and 14 imputed SNPs in the SPRY1 gene and obesity-related traits and osteoporosis in a Korean women cohort (3013 subjects). RESULTS All four SPRY1 gene SNPs were significantly associated with either obesity-related traits or osteoporosis. The TGCC haplotype in the SRPY1 gene showed simultaneous association with an increased risk for obesity-related traits, percentage body fat (p=0.0087) and percentage abdominal fat (p=0.047), and osteoporosis (odds ratio=1.50; p=0.025) in the recessive genetic model. CONCLUSIONS Our results support a previous finding in conditional Spry1 gene knockout mice and suggest that the SPRY1 gene is an important genetic factor for determining the risk of both obesity and osteoporosis in humans.

Replicated association between genetic variation in the PARK2 gene and blood pressure

BACKGROUND The PARK2 gene encodes Parkin which is linked to the mitochondrial fusion, fission and mitophagy. In the previous study, single nucleotide polymorphisms (SNPs) in the PARK2 gene have been reported to be associated with blood pressure (BP) in Nigerian families. We aimed to confirm whether the genetic variation of the PARK2 gene influenced the susceptibility to BP and hypertension in Korean population. METHODS We performed the quantitative BP trait analysis and hypertension case-control analysis for the 227 SNPs in the PARK2 gene in the Korean Association Resource (KARE) cohort (8512 subjects) and the Korean Urban Epidemiology (KUE) cohort (3703 subjects) by the independent association analysis and meta-analysis. RESULTS Two SNPs, rs9456721 and rs6902041, were significantly associated with systolic BP (SBP) and diastolic BP (DBP), respectively, in the KARE subjects, and their association p-values were below the Bonferroni-corrected significance level. The replication analysis in the KUE subjects revealed a significant association between the SNP, rs6902041 and BP. CONCLUSIONS These results indicate that genetic variation in the PARK2 gene is significantly associated with BP not only in the Nigerian population but also in the Korean population. This study may provide insight into the genetic basis of hypertension related to the mitochondrial quality control.

Bore-Sight Calibration of Multiple Laser Range Finders for Kinematic 3D Laser Scanning Systems

The Simultaneous Localization and Mapping (SLAM) technique has been used for autonomous navigation of mobile systems; now, its applications have been extended to 3D data acquisition of indoor environments. In order to reconstruct 3D scenes of indoor space, the kinematic 3D laser scanning system, developed herein, carries three laser range finders (LRFs): one is mounted horizontally for system-position correction and the other two are mounted vertically to collect 3D point-cloud data of the surrounding environment along the system’s trajectory. However, the kinematic laser scanning results can be impaired by errors resulting from sensor misalignment. In the present study, the bore-sight calibration of multiple LRF sensors was performed using a specially designed double-deck calibration facility, which is composed of two half-circle-shaped aluminum frames. Moreover, in order to automatically achieve point-to-point correspondences between a scan point and the target center, a V-shaped target was designed as well. The bore-sight calibration parameters were estimated by a constrained least squares method, which iteratively minimizes the weighted sum of squares of residuals while constraining some highly-correlated parameters. The calibration performance was analyzed by means of a correlation matrix. After calibration, the visual inspection of mapped data and residual calculation confirmed the effectiveness of the proposed calibration approach.

Concurrent TSHR mutations and DIO2 T92A polymorphism result in abnormal thyroid hormone metabolism

Deiodinase 2 (DIO2) plays an important role in thyroid hormone metabolism and its regulation. However, molecular mechanism that regulates DIO2 activity remains unclear; only mutaions in selenocysteine insertion sequence binding protein 2 and selenocysteine tranfer RNA (tRNA[Ser]Sec) are reported to result in decreased DIO2 activity. Two patients with clinical evidence of abnormal thyroid hormone metabolism were identified and found to have TSHR mutations as well as DIO2 T92A single nucleotide polymorphism (SNP). Primary-cultured fibroblasts from one patient present a high level of basal DIO2 enzymatic activity, possibly due to compensation by augmented DIO2 expression. However, this high enzymatic active state yet fails to respond to accelerating TSH. Consequently, TSHR mutations along with DIO2 T92A SNP (“double hit”) may lead to a significant reduction in DIO2 activity stimulated by TSH, and thereby may have clinical relevance in a select population of hypothyroidism patients who might benefit from a T3/T4 combination therapy.